Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
12(GU)
STATEMENT OF INTENT
This guideline is meant to be a guide for clinical practice, based on the best
available evidence at the time of development. Adherence to this guideline may
not necessarily guarantee the best outcome in every case. Every health care
provider is responsible for the management of his/her unique patient based on
the clinical picture presented by the patient and the management options
available locally.
This guideline was issued in 2011 and will be reviewed in 2016 or sooner if
new evidence becomes available
CPG Secretariat
c/o Health Technology Assessment Unit
Medical Development Division
Ministry of Health Malaysia
4th floor, Block E1, Parcel E
62590, Putrajaya.
ii
iv
This involves comparing current practice with the recommendations. The audit
criteria will help this baseline assessment.
We have identified several goals for implementation based on the key priorities
for implementation identified in the guideline
vi
vii
viii
EXTERNAL REVIEWERS
1)
2)
3)
4)
5)
Dr Tai Li Ling
Consultant Intensivist
Department of Anaesthesia and Intensive Care
Hospital Kuala Lumpur.
ix
SUMMARY
KEY MESSAGES
1
In patients with permanent AF, who need treatment for rate control, betablockers or rate-limiting calcium antagonists should be the preferred initial
monotherapy in all patients while digoxin should only be considered as
monotherapy in predominantly sedentary patients.
The management cascade for patients with AF. ACEI = angiotensin-converting enzyme inhibitor; AF = atrial
fibrillation; ARB = angiotensin receptor blocker; PUFA = polyunsaturated fatty acid; TE = thrombo-embolism.
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart
Journal 2010; doi:10.1093/eurheartj/ehq278)
xi
<<ATRIAL
<<ATRIAL
FIBRILLATION
FIBRILLATION
MANAGEMENT
MANAGEMENT
CASCADE>>
CASCADE>>
Grading
Grading
System
System
The
The
format
format
used
used
forfor
Classification
Classification
of of
Recommendations
Recommendations
andand
Level
Level
of of
Evidence
Evidence
was
was
adapted
adapted
from
from
thethe
American
American
Heart
Heart
Association
Association
andand
thethe
European
European
Society
Society
of of
Cardiology.
Cardiology.
GRADES
GRADES
OFOF
RECOMMENDATIONS
RECOMMENDATIONS
AND
AND
LEVELS
LEVELS
OFOF
EVIDENCE
EVIDENCE
GRADES
OFOF
RECOMMENDATION
GRADES
RECOMMENDATION
I I
II II
Conditions
which
there
is evidence
and/or
general
agreement
Conditions
forfor
which
there
is evidence
and/or
general
agreement
a given
procedure/therapy
is beneficial,
useful
and/or
thatthat
a given
procedure/therapy
is beneficial,
useful
and/or
effective.
effective.
Conditions
forfor
which
there
is conflicting
evidence
and/or
Conditions
which
there
is conflicting
evidence
and/or
divergence
of opinion
about
thethe
usefulness/efficacy
of aof a
divergence
of opinion
about
usefulness/efficacy
procedure/therapy.
procedure/therapy.
II-aII-a
Weight
of evidence/opinion
is in
of its
usefulness/efficacy.
Weight
of evidence/opinion
is favor
in favor
of its
usefulness/efficacy.
II-bII-b
Usefulness/efficacy
is less
well
established
by by
evidence/opinion
Usefulness/efficacy
is less
well
established
evidence/opinion
III III
Conditions
forfor
which
there
is evidence
and/or
general
agreement
Conditions
which
there
is evidence
and/or
general
agreement
thatthat
a procedure/therapy
is not
useful/effective
andand
in some
a procedure/therapy
is not
useful/effective
in some
cases
may
be be
harmful.
cases
may
harmful.
LEVELS
OFOF
EVIDENCE
LEVELS
EVIDENCE
A A
B B
C C
Data
derived
from
multiple
randomised
clinical
trials
or meta
Data
derived
from
multiple
randomised
clinical
trials
or meta
analyses
analyses
Data
derived
from
a single
randomised
clinical
trialtrial
or large
nonnon
Data
derived
from
a single
randomised
clinical
or large
randomised
studies
randomised
studies
Only
consensus
of opinions
of experts,
case
studies
or standard
Only
consensus
of opinions
of experts,
case
studies
or standard
of care
of care
xii
TABLE OF CONTENTS
Statement of Intent
Foreword
About the Guideline
Guideline Development Process
Guideline Working Group
External Reviewer
Summary
Key Messages
Atrial Fibrillation Management Cascade
Grading System
Table of Content
I. Introduction
1.1 Definition
1.2 Types of Atrial Fibrillation
1.3 AF Natural Time Course
1.4 Epidemiology and Prognosis
2.
Pathophysiology
2.1. Clinical Aspects
2.1.1. Causes and Associated Conditions
3.
Initial Management
3.1. Clinical History and Physical Examination and Investigations
3.1.1. Detection
3.1.1.1. Electrocardiogram
3.1 Diagnostic Evaluation
3.2 Echocardiogram
3.3 Clinical Follow-up
4 Management Principles
4.1 General Principles
4.2 Thromboembolic Prophylaxis
4.3 Heart Rate vs Rhythm Control
5 Management Acute-onset AF
5.1 Acute AF In Hemodynamically Unstable Patients
5.1.1 Acute Rate Control
5.1.2 Pharmacological Cardioversion
5.1.2.1
Pill-in-the-pocket Approach
5.1.3 Direct Current Cardioversion
5.1.3.1
Procedure
5.1.3.2
Complications
5.1.3.3
Cardioversion In Patients With Implanted
Pacemakers And Defibrillators
5.1.3.4
Recurrence After Cardioversion
5.1.4 Antithrombotic Therapy For Acute-onset AF
6 Management - Prevention of Thromboembolism
xiii
xiv
9.1 Post-Operative AF
9.1.1 Prevention Of Post-operative AF
9.1.2 Treatment of Post-operative AF
9.2 Acute Coronary Syndrome
9.3 Wolff-Parkinson-White (WPW) Pre-excitation Syndromes
9.3.1 Sudden Death And Risk Stratification
9.4 Hyperthyroidism
9.5 Pregnancy
9.6 Hypertrophic Cardiomyopathy
9.7 Pulmonary Diseases
9.8 Heart Failure
9.9 Athletes
9.10 Valvular Heart Disease
10 Referrals
11 Audit and Evaluation
Appendixes
Glossary
References
xv
1 INTRODUCTION
1.1 DEFINITION
Atrial fibrillation (AF) is an atrial tachyarrhythmia characterized by uncoordinated
atrial activation with consequent deterioration of atrial mechanical function. The
surface ECG is characterized by absolutely irregular RR intervals and the
absence of any distinct P waves. The P waves are replaced by fibrillary (F)
waves.
Atrial Flutter (AFl) in the typical form is characterized by a saw-tooth pattern of
regular atrial activation called flutter (F) waves on the ECG. AFl commonly
occurs with 2:1 AV block, resulting in a regular or irregular ventricular rate of 120
to 160 beats per minute (most characteristically about 150 beats per minute).
1.2 TYPES OF ATRIAL FIBRILLATION
Clinically, five types of AF are recognized based on the presentation and the
duration of the episode. These categories are set out below. (See Table 1 and
Figure 2)
<<Table 1 >>
The term
lone AF applies to young
individuals
Terminology
Clinical
Features (under 60 years of age)
Patternwithout
clinical
or(first
echocardiographic
Initial event
Symptomaticevidence of cardiopulmonary disease,
May or mayincluding
not recur
detected episode) These Asymptomatic
hypertension.
patients have a favourable prognosis with respect to
Onset unknown
thromboembolism
andSpontaneous
mortality. termination <7 days and most often < Recurrent
Paroxysmal
48 hours
Persistent
Not self terminating
Recurrent
Silent
AF being asymptomatic
is detected by an opportunistic
ECG or may
Lasting >7 days or requiring cardioversion for
present as an AF-related
complication such as ischemic stroke.
termination
Long standing persistent
Recurrent
Permanent
Not terminated
Terminated but relapsed
No cardioversion attempt
Established
1 yearfor
when
it is decided
to adopt a rhythm
control
This classication is useful
clinical
management
of AF
patients (Figure 1),
strategysymptoms are also considered.
especially when AF-related
<<Figure 1>>
<<Figure
Adapted
from 1>>
the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart
<<Figure
1>>
Journal 2010; doi:10.1093/eurheartj/ehq278)
1.3 AF NATURAL TIME COURSE
1.3 AF NATURAL TIME COURSE
Figure22: :Natural
Naturaltime
timecourse
courseof
of AF.
AF. AF
AF == atrial
atrial fibrillation.
fibrillation. The dark blue boxes show aa typical
Figure
typical sequence
sequence of
of
periodsininAF
AF against
against aa background
background of
of sinus
sinus rhythm,
rhythm, and
and illustrate the progression of
periods
of AF
AF from
from silent
silent and
and
undiagnosedtotoparoxysmal
paroxysmal and
and chronic
chronic forms,
forms, at
at times
times symptomatic. The upper bars
undiagnosed
bars indicate
indicate therapeutic
therapeutic
measures that
that could
could be
be pursued.
pursued. Light
Light blue
blue boxes
boxes indicate
indicate therapies that have proven
measures
proven effects
effects on
on hard
hard
Asymptomatic
AF
is
common
even
in Red
symptomatic
irrespective
of
outcomesininAF,
AF,such
such
asstroke
stroke
or acute
acute heart
heart
failure.
Red
therapies that
are
outcomes
as
or
failure.
boxes indicatepatients,
that
are currently
currently used
used
forsymptom
symptom
relief,
but may
may
in the
the future
futurewas
contribute
to reduction
reduction
Rate
for
relief,
but
in
contribute
to
of AF-related complications.
complications.
Rate control
control
whether
the
initial
presentation
persistent
or paroxysmal.
This has important
(greybox)
box)isisvaluable
valuable
forsymptom
symptomaimed
relief and
and
may
improve cardiovascular
outcomes.
(grey
for
relief
improve
implications
for strategies
atmay
preventing
AF-related
complications.
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart
<<Figure
Journal 2010;2>>
doi:10.1093/eurheartj/ehq278)
Relative change in AF
patients
Outcome parameter
2. Stroke (includes
haemorrhagic
stroke and
<<Figure
2>>
cerebral bleeds)
1.4
AND PROGNOSIS AF patients and may contribute
3. EPIDEMIOLOGY
Hospitalizations
Data capacity
from predominantly western populations suggest the estimated prevalence
through palpitations and other
of AF is 0.4% to 1% in the general population. The prevalence of AF doubles with
AF-related
each decade of age, from 0.5% at age 50-59
years tosymptoms.
almost 9% at age 80-89
years.3-4
2. PATHOPHYSIOLOGY
Understanding the pathophysiology of atrial brillation (AF) requires integration
of
information
from
clinical,
histological,
electrophysiological
and
echocardiographic sources. There is no single cause or mechanism that results
in AF, and it may present in a multitude of ways.
2.1 CLINICAL ASPECTS
There are many risk factors for developing AF. In the Framingham study the
development of AF was associated with increasing age, diabetes, hypertension
and valve disease. It is also commonly associated with, and complicated by HF
and strokes.
2.1.1 CAUSES AND ASSOCIATED CONDITIONS
AF is often associated with co-existing medical conditions. The underlying
conditions and factors predisposing patients to AF are listed in Table 3.
<<Table 3 >>
Table 3: Common cardiac and non-cardiac risk factors of AF.
Does the heart rhythm during the episode feel regular or irregular?
The
EHRA any
symptom
score (seefactor
Tablesuch
5) provides
a simpleemotion,
clinical tool
Is there
precipitating
as exercise,
or for
assessing symptoms during AF. The score only considers symptoms that are
alcohol intake?
attributable to AF and reverse or reduce upon restoration of sinus rhythm or with
effective rate control.
Are the episodes frequent or infrequent, and are they long or short
3.1.1
DETECTION
lasting?
disease?
With the above in mind, a thorough medical history should be obtained from the
patient with suspected or known AF (see Table 4).
<<Table 4>>
3 INITIAL MANAGEMENT
The EHRA symptom score (see Table 5) provides a simple clinical tool for
3.1 CLINICAL HISTORY, PHYSICAL EXAMINATION AND INVESTIGATIONS
assessing symptoms during AF. The score only considers symptoms that are
attributable to AF and reverse or reduce upon restoration of sinus rhythm or with
The acute management of AF patients should concentrate on
effective rate control.
Relief of symptoms
Assessment of AF-associated risk
<<Table 5 >>
Determination of the European Heart Rhythm Association (EHRA) score
Table 5 : EHRA score of AF-related symptoms
(Table 5, page 7)
Estimation of stroke risk (see Section 6.1, page 26)
Search
for conditions of
that
predisposesymptoms
to AF (see Section
page 5) and
Classification
AF-related
(EHRA2.1.1,
score)
3.1.1 DETECTION
Search for complications of the arrhythmia (see Section 1.4, page 3)
Explanation
EHRAwith
class
Those
undiagnosed AF can receive treatment sooner if an opportunistic
With the above in mind, a thorough medical history should be obtained from the
case finding is undertaken. Routine palpation of the radial pulse (not less than 20
patient
with
suspected
or known
AF (see Table 4).
No
symptoms
EHRA
I
seconds) during screening
of blood pressure will be a good opportunity to pick up
undiagnosed atrial fibrillation.
<<Table
EHRA 4>>
II
Mild symptoms; normal daily activity not affected
3.1.1 DETECTION
Those with undiagnosed AF can receive treatment sooner if an opportunistic
case finding is undertaken. Routine palpation of the radial pulse (not less than 20
seconds) during screening of blood pressure will be a good opportunity to pick up
undiagnosed atrial fibrillation.
In patients presenting with any of the following:
x breathlessness/dyspnoea,
x palpitations,
x syncope/dizziness,
x chest discomfort or stroke/TIA,
manual pulse palpation should be performed to assess for the presence of an
irregular pulse that may indicate AF.
3.1.1.1 ELECTROCARDIOGRAM
The diagnosis of AF requires confirmation by ECG, sometimes in the form
of bedside telemetry, ambulatory Holter recordings and event loop
recordings. 2, 10
If AF is present at the time of recording, a standard 12-lead ECG is sufficient to
confirm the diagnosis. In paroxysmal AF, 7-days Holter ECG recording or daily
and symptom-activated event recordings may document the arrhythmia in 70% of
AF patients.2
The search for AF should be intensified;
7 including prolonged monitoring, when
patients
x Is the rate control approach working properly; has the target for heart rate
at rest and during exercise been reached?
The diagnosis of AF requires documentation by ECG.2,10
10
In patients with suspected AF, an attempt to record an ECG should be made
Keypoints
x Is the rate control approach working properly; has the target for heart rate
at rest and during exercise been reached?
I BIB
I BIB
I BIB
I CIC
I BIB
I CIC
IIaB
IIa B
IIaB
IIa
B
IIaC
IIa
C
In patients with AF treated with rate control, Holter ECG monitoring should be
considered for assessment of rate control or bradycardia.
IIa
C
IIaC
In young active patients with AF treated with rate control, exercise testing should
be considered in order to assess ventricular rate control.
IIaC
IIa
C
IIaC
IIa
C
IIaC
IIa C
IIbB
IIb
B
IIbC
IIb C
Most patients with AF may benet from specialist follow-up at regular intervals.
<<Figure 3>>
11
12
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/ehq278)
Figure 3: Choice of rate and rhythm control strategies. Rate control is needed for most patients with AF unless the heart rate during AF is naturally slow. Rhythm
control may be added to rate control if the patient is symptomatic despite adequate rate control, or if a rhythm control strategy is selected because of factors such
as the degree of symptoms, younger age, or higher activity levels. Permanent AF is managed by rate control unless it is deemed possible to restore sinus rhythm
when the AF category is re-designated as long-standing persistent. Paroxysmal AF is more often managed with a rhythm control strategy, especially if it is
symptomatic and there is little or no associated underlying heart disease. Solid lines indicate the first-line management strategy. Dashed lines represent fall-back
objectives and dotted lines indicate alternative approaches which may be used in selected patients.
4. MANAGEMENT PRINCIPLES
4.1 GENERAL PRINCIPLES
In patients with AF or AFI, the aims of treatment involve the following five
objectives.
I
For rate and rhythm control, drugs remain the first choice. Radiofrequency
ablation may be considered in symptomatic AF and in lone AF to avoid long-term
drug therapy. In selected individuals undergoing cardiac surgery, surgical maze
procedure may be a therapeutic option.
4.2 THROMBOEMBOLIC PROPHYLAXIS
Antithrombotic therapy must be considered in all patients with AF. Strategies that
may reduce thromboembolic risk include the following treatments:
Anticoagulants such as Vitamin K Antagonist,
Antiplatelet agents, such as aspirin and clopidogrel
Intravenous (IV) heparin or low molecular weight heparin (LMWH)
Left atrial appendage (LAA) occlusion, either surgically or percutaneously.
The decision regarding the method of reduction in the risk of stroke, should take
into account both the persons risk of thromboembolism and their risk of bleeding.
It is important to remember that vitamin K antagonist such as Warfarin is very
effective and reduces the risk of stroke overall by two thirds. (For details see
Section 6, page 26)
4.3. HEART RATE CONTROL VERSUS RHYTHM CONTROL
Rate control involves the use of chronotropic drugs or electrophysiological or
surgical interventions to reduce the rapid heart rate (ventricular rate) often found
in patients with AF. Although the atria continue to fibrillate with this strategy, it is
nonetheless thought to be an effective treatment as it improves symptoms and
reduces the risk of associated morbidity. However, the persistence of the
arrhythmia continues the risk of stroke and thromboembolic events occurring.
Administering antithrombotic drugs reduces this risk. (See Figure 3, page 12)
Rhythm control involves the use of electrical or pharmacological cardioversion or
electrophysiological or surgical interventions to convert the arrhythmia associated
with AF to normal sinus rhythm. Patients who have been successfully
cardioverted are generally administered antiarrhythmic drugs for the long term to
help prevent the recurrence of AF. The rhythm control strategies also require the
appropriate administration of antithrombotic therapy to reduce the risk of stroke
and thromboembolic events occurring.
Randomized trials comparing outcomes of rhythm versus rate control strategies
in patients with AF are summarized in Table 7 and 8.22-28
<<Table 7>>
<<Table 8>>
14
15
23
24
25
26
27
28
AFFIRM (2002)
RACE (2002)
STAF (2003)
HOTCAFE (2004)
AF-CHF (2008)
J-RHYTHM (2009)
823
1376
205
200
522
4060
252
Patients
(n)
64.7
66
60.8
66.0
68.0
69.7
61.0
Mean
age
(years)
1.6
3.1
1.7
1.6
2.3
3.5
1.0
Mean
follow-up
(years)
Paroxysmal AF
Persistent AF
(>4 weeks and
<2 years), LA size
>45 mm, CHF NYHA
IIIV, LVEF <45%
First clinically overt
persistent AF (>7 days
and <2 years),
age 5075 years
LVEF <35%, symptoms
of CHF, history of AF
(>6 h or
DCC <last 6 months)
Persistent AF
(7360 days)
Paroxysmal AF or
persistent AF, age >65
years, or risk of stroke or
death
Inclusion criteria
182/1376
(27%)
175/1376
(25%)
89/405
(22.0%)
Cardiovascular death
Composite of total
mortality, symptomatic
cerebral infarction,
systemic embolism, major
bleeding, hospitalization for
heart failure, or physical/
psychological disability
64/418
(15.3%)
4/104
(3.9%)
1/101
(1.0%)
Composite: death,
thrombo-embolic events;
intracranial/major
haemorrhage
9/100
(9.0%)
60/266
(22.6%)
10/100
(10.0%)
44/256
(17.2%)
Composite: cardiovascular
death, CHF, severe bleeding,
pacemaker implantation,
thrombo-embolic events,
severe adverse effects of
antiarrhythmic drugs
356/2033
(26.7%)
Composite: overall
mortality, cerebrovascular
complications, CPR, embolic
events
310/2027
(25.9%)
0.012
0.59
> 0.71
0.99
0.11
0.08
All-cause mortality
Symptomatic improvement
AF = atrial fibrillation; AFFIRM = Atrial Fibrillation Follow-up Investigation of Rhythm Management; CHF = congestive heart failure; CPR = cardiopulmonary
resuscitation; DCC = direct current cardioversion; HOT CAFE = How to Treat Chronic Atrial Fibrillation; J-RHYTHM = Japanese Rhythm Management Trial for
Atrial Fibrillation; LVEF = left ventricular ejection fraction; NYHA = New York Heart Association; PIAF = Pharmacological Intervention in Atrial Fibrillation; RACE =
RAte Control versus Electrical cardioversion for persistent atrial fibrillation; STAF = Strategies of Treatment of Atrial Fibrillation.
22
Ref
PIAF (2000)
Trial
Table 7: General characteristic s of rhythm control and rate control trials in patients with AF
16
25
26
27
STAF (2003)
AF-CHF (2008)
228/217
4 (1/3)
12 (8/4)
36
666 (310/356)
175/182
0/2
8/3
18/18
167/164
1/1
Deaths from
cardiovascular
causes
53/35
1/1
0/1
ND
113/165
11/9
0/3
1/5
ND
77/80
ND
Stroke
ND
ND
ND
14/21
ND
ND
Thrombo-embolic
events
ND
5/8
8/1
12/9
107/96
ND
Bleeding
23
24
RACE (2002)
22
PIAF (2000)
AFFIRM (2002)
Ref
Trial
Table 8: Comparison of adverse outcomes in rhythm control and rate control trials in patients with AF
The consistent nding in all ve studies was that rhythm control offered no
survival advantage and, in most cases, had little effect on morbidity and quality of
life. However, it should be emphasised that these conclusions are not necessarily
applicable to all groups of patients. The ve recent studies enrolled mostly older
patients with additional risk factors for stroke, many of whom also had heart
failure. Younger patients with normal hearts and primarily paroxysmal atrial
brillation (PAF) were not well represented. Importantly, in a predened subgroup
of AFFIRM participants aged less than 65 years, hazard ratios for death showed
a paradoxical trend towards superiority of the rhythm-control strategy.
The initial therapy after onset of AF should always include adequate
antithrombotic treatment and control of the ventricular rate. If the ultimate goal is
restoration and maintenance of sinus rhythm, rate control medication should be
continued throughout follow-up, unless continuous sinus rhythm is present. The
goal is to control the ventricular rate adequately whenever recurrent AF occurs.
The decision to add rhythm control therapy to the management of AF requires an
individual decision and should therefore be discussed at the beginning of AF
management. Before choosing rate control alone as a long-term strategy, the
clinician should consider how permanent AF is likely to affect the individual
patient in the future and how successful rhythm control is expected to be (Figure
3, page 12). Symptoms related to AF are an important determinant in making the
decision to opt for rate or rhythm control (e.g. globally assessed by the EHRA
score, Table 5, page 7), in addition to factors that may inuence the success of
rhythm control. The latter include a long history of AF, older age, more severe
associated cardiovascular diseases, other associated medical conditions, and
enlarged LA size.
A rate-control strategy should be the preferred initial option in the following
patients with persistent AF:
x Over 65 years old
x With coronary artery disease and/or left ventricular dysfunction
x With contraindications to antiarrhythmic drugs
x Unsuitable for cardioversion*
A rhythm-control strategy should be the preferred initial option in the following
patients with persistent AF:
x Those who are symptomatic
x Younger patients
x Those presenting for the first time with lone AF
x Those with AF secondary to a treated/corrected precipitant
Keypoints
IA
IA
Rate control should be the initial approach in elderly patients with AF and minor
symptoms (EHRA class 1).23,24,27
IBIB
IA
IA
IIaC
IIaC
IIaC
IIaC
IIac
IIaC
IIaB
IIaB
5. MANAGEMENT ACUTE-ONSET AF
5. MANAGEMENT ACUTE-ONSET AF
The majority of patients who present with AF are hemodynamically stable but
there is a small
group of
of patients
whopresent
are significantly
compromised
by the
onset
The majority
patients who
with AF are
hemodynamically
stable
but
of AF. These
hospitalization
urgent intervention
therepatients
is a smallrequire
group ofimmediate
patients who
are significantlyand
compromised
by the onset
to preventoffurther
deterioration.
AF. These
patients require immediate hospitalization and urgent intervention
to prevent further deterioration.
5.1.1 ACUTE
CONTROL
5.1.1RATE
ACUTE
RATE CONTROL
It is important
to understand
that inthat
these
circumstances
the the
slow
onset
It is important
to understand
in these
circumstances
slow
onsetofof
digoxin makes
inappropriate
for useforinuse
thisin situation.
Patients
whose
digoxinit makes
it inappropriate
this situation.
Patients
whoseAFAFisis
associatedassociated
with thyrotoxicosis
will not
to any
measures
with thyrotoxicosis
will respond
not respond
to any
measuresuntil
untilthe
the
underlyingunderlying
thyroid disease
is first treated.
Patients
with with
accessory
pathway
such
thyroid disease
is first treated.
Patients
accessory
pathway
such
as the Wolff-Parkinson-White
(WPW)(WPW)
syndrome
are particularly
at risk
following
as the Wolff-Parkinson-White
syndrome
are particularly
at risk
following
of AF because
theypresent
can present
rapid
ventricularrates
rates
the onset the
of onset
AF because
they can
with with
very very
rapid
ventricular
(greater
bpm)
and
mayspecific
need specific
management.
(greater than
200 than
bpm)200
and
may
need
management.
Whenpresent
patients with
present
with unacceptably
high ventricular
primary
aimisis
When patients
unacceptably
high ventricular
raterate
the the
primary
aim
of rate control.
one of rateone
control.
AF with
slow ventricular
rates
may respond
to atropine
2 mg
i.v.),
many
AF with slow
ventricular
rates may
respond
to atropine
(0.5 (0.5
2 mg
i.v.),
butbut
many
patients with symptomatic bradyarrhythmia may require either urgent placement
patients with symptomatic bradyarrhythmia may require either urgent placement
of a temporary pacemaker lead in the right ventricle and/or cardioversion.
of a temporary pacemaker lead in the right ventricle and/or cardioversion.
Acute initiation of rate control therapy should usually be followed by a long-term
Acute initiation
of rate
controldetails
therapy
should
followed
by a7 on
long-term
rate control
strategy;
of drugs
and usually
doses arebegiven
in Section
page 66.
rate control strategy; details of drugs and doses are given in Section 7 on page 66.
Keypoints
In the acute setting in the absence of pre-excitation, i.v. administration of -
IA acute
blockers
calcium channeli.v.
antagonists
is recommended
to
In the
settingorinnon-dihydropyridine
the absence of pre-excitation,
administration
of the ventricular response
to AF,
exercising
caution in is
patients
with
blockers orslow
non-dihydropyridine
calcium
channel
antagonists
recommended
to
34
hypotension
or heart failure.
slow the ventricular
response
to AF, exercising caution in patients with
IBIB
IC
IB
ICIC
IIIC
IIIC
Table 9 : Intravenous pharmacological agents for acute control of ventricular rate in AF/AFL
In the presence
of other
abnormalities (e.g.
hypertensive
disease,
Commonly
Onsetcardiac
of
Commonly-used
Adverse
Limitationsheart
Commonlyusedheart
loadingdisease),
action
effects ventricular ratesused
oralstill
valvular
onset of maintenance
AF
with acceptable
may
dose (IV)
dose (IV)
maintenance
compromised cardiac function. While rate control is unlikely to bring about
clinical
dose for
longterm rate
improvement in these circumstances, there is a need for the restorationcontrol
of sinus
Beta-blockers rhythm.
Drug
Esmolol
0.5 mg/kg
(very shortover 1 min
acting) Pharmacological
5 min
Hypotension,
Negative
Oral
heart block,
inotropic
preparation
cardioversion ofkg/min
AF infusion
may be initiated
administration
bradycardia,by a bolus
effect
not available
asthma,
heart with antiarrhythmic drugs
of an antiarrhythmic drug. Although the conversion
rate
failure
is lower than with direct current cardioversion (DCCV), it does not require
Metoprolol conscious sedation or anesthesia, and may facilitate the choice
23.75 to 200
In people
of antiarrhythmic
mg/day
with heart
drug therapy to prevent recurrent AF.
(divided doses)
failure, lower
doses may
be advisable.
failure, lower
doses may
be advisable.
Negative
inotropic
effect
common agent
<<Table 10>>
(once daily
longacting)
0.075 to 0.15
to 5 min
120 to 360 mg/
In clinical
practice, 3 amiodarone
isN/Athe most
used
in the
mg/kg over 2 min
day (divided
doses or once
management of patients presenting in AF with haemodynamic compromise,
as it
daily longappears to have a hybrid
effect
of
rapid
reduction
in
ventricular
rate
in
acting)most
34
hypotension
or heart
patients
with failure.
a proportion of these reverting to sinus rhythm over a longer period.
Other
Verapamil
Digoxin
IB
0.25 to 1.0
2 hr
0.125 to 0.25
Digoxin
over 20 min
(10 min to
4 hours)
infusion
back pain,
heart block,
N/A
0.0625 to 0.375
mg
toxicity, heart
mg/day
In the acute
setting,
i.v. administration of mg/day
amiodarone
is recommended to
control
<<Figure
4>>
block,
(individualise
bradycardia
the heart rate in patients with AF and concomitant heart
failure, or in thedosage)
setting
35
of hypotension.
Amiodarone
5 mg/kg
Variable
50 mg/hour
Hypotension,
N/A
100 to 200
mg/day
IC
IIIC
<<Table 9>>
5.1.2 PHARMACOLOGICAL CARDIOVERSION
In the presence of other cardiac abnormalities (e.g. hypertensive heart disease,
valvular heart disease), onset of AF with acceptable ventricular rates may still
compromised cardiac function. While rate control is unlikely to bring about clinical
improvement in these circumstances, there is a need for the restoration of sinus
rhythm.
Pharmacological cardioversion of AF may be initiated by a bolus administration
of an antiarrhythmic drug. Although the 19
conversion rate with antiarrhythmic drugs
is lower than with direct current cardioversion (DCCV), it does not require
hypotension
or heart
failure.34 of AF may be initiated by a bolus administration
Pharmacological
cardioversion
of an antiarrhythmic drug. Although the conversion rate with antiarrhythmic drugs
In
acute
setting,
administration
of amiodarone
is recommended
to control
is the
lower
than
with i.v.
direct
current cardioversion
(DCCV),
it does not
require
the
heart rate
in patients
with AF and
heart
failure, of
or antiarrhythmic
in the setting
conscious
sedation
or anesthesia,
andconcomitant
may facilitate
the choice
35
of
hypotension.
drug
therapy to prevent recurrent AF.
In
pre-excitation,
preferred
drugs
are class I antiarrhythmic
drugs
(Seecontinuous
Appendix
Most
patients who
undergo
pharmacological
cardioversion
require
D)
or amiodarone.
medical
supervision and ECG monitoring during the drug infusion and for a
period afterwards (usually about half the drug elimination half-life) to detect
pre-excited
is as
present,
-blockers,
non-dihydropyridine
calcium
When
proarrhythmic
eventsAFsuch
ventricular
proarrhythmia,
sinus node arrest,
or
atrioventricular
block.digoxin, and adenosine are contraindicated.
channel
antagonists,
Several agents
<<Table
9>> are available for pharmacological cardioversion (see Table 10 on
page 20).
5.1.2 PHARMACOLOGICAL CARDIOVERSION
<<Table 10>>
Table
10: presence
Drug and doses
pharmacological
conversion of (recent-onset)
AF
In the
of for
other
cardiac abnormalities
(e.g. hypertensive
heart disease,
In clinical
practice,
amiodarone
is with
the acceptable
most common
agentrates
usedmay
in still
the
valvular
heart
disease),
onset of AF
ventricular
management
patients
presenting
AF control
withdose
haemodynamic
compromise,
as it
compromised
cardiac
function.
Whileinrate
is unlikely to bring
Drug of
Dose
Follow-up
Riskabout clinical
appears
to have
a 5hybrid
rapid
in
rate
in
most
Amiodarone
mg/kg
i.veffect
over 1h of 50mg/kg
Willof
slow
improvement
in these
circumstances,
there reduction
is a needPhlebitis,
for ventricular
thehypotension.
restoration
sinus
the ventricular
Delayedperiod.
AF
patients with a proportion of these reverting to sinus rhythm
over rate.
a longer
rhythm.
conversion to sinus rhythm.
Flecainide
200-300 mg p.o
N/A
Not suitable for patients with
<<Figure 4>> cardioversion of AF may be initiatedmarked
Pharmacological
by astructural
bolus administration
heart disease,
maywith
prolong
QRS duration, and
of an antiarrhythmic drug. Although the conversion rate
antiarrhythmic
drugs
hence theitQTdoes
interval;not
and may
is lower than with direct current cardioversion (DCCV),
require
inadvertently increase the
conscious sedation or anesthesia, and may facilitate the
choice
antiarrhythmic
ventricular
rateof
due
to conversion
drug therapy to prevent recurrent AF.
to atrial flutter and 1:1 conduction
to the ventricles.
Propafenone
mg p.o
Not suitable for patients with
Most
patients who 450-600
undergo
pharmacological cardioversion
require continuous
marked structural heart
medical supervision and ECG monitoring during the
drugmay
infusion
and for a
disease;
prolong QRS
duration; willhalf-life)
slightly slowto detect
period afterwards (usually about half the drug elimination
the ventricular
but may
proarrhythmic events such as ventricular proarrhythmia,
sinus rate,
node
arrest, or
inadvertently increase the
atrioventricular block.
ventricular rate due to conversion
to atrial flutter and 1:1 conduction
to the ventricles.
Several agents are available for pharmacological cardioversion
(see Table 10 on
page 20).
<<Table 10>>
In clinical practice, amiodarone is the most common agent used in the
management of patients presenting in AF with haemodynamic compromise, as it
appears to have a hybrid effect of rapid reduction in ventricular rate in most
patients with a proportion of these reverting to sinus rhythm over a longer period.
Adapted with modification from the ESC Guidelines for the Management of Atrial
<<Figure 4>>
Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/
ehq278)
20
21
oral flecainide
oral propefenone
i.v amiodarone
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/ehq278)
Figure 4 Direct current conversion and pharmacological cardioversion of recent-onset AF in patients considered for pharmacological cardioversion. AF= atrial
fibrillation
No
Electrical cardioversion
Yes
No
Yes
Haemodynamic instability
Keypoints
When
pharmacological
cardioversion
is or
preferred
and there
is no
structural
propafenone (when
there is little
no underlying
structural
heart
disease)heart
or i.v
When pharmacological
cardioversion
preferred
and there
is
structural
disease,
oral
ecainide
or propafenone
is isrecommended
forno4,
cardioversion
of
amiodarone
(when
there
is is
structural
disease)
(Figure
21).heart
The
When36-38
pharmacological
cardioversion
preferred
and
there is
nopage
structural
heart
IA
disease,
oral
ecainide
or
propafenone
is
recommended
for
cardioversion
of
anticipated
conversion
rateoris propafenone
50% within ~15
120 min.
recent-onset
AF.
disease,
oral
ecainide
is
recommended
for
cardioversion
of
recent-onsetrecent-onset
AF.36-38 AF.36-38
In patients with recent-onset AF and structural heart disease, i.v. amiodarone is
pharmacological
preferred
and disease,
there i.v.
is no
structural
heart
39-41
In patients
with recent-onset
andisstructural
i.v.
amiodarone
In
patients When
with
recent-onset
AFcardioversion
and AF
structural
heart heart
disease,
amiodarone
isis
recommended.
IAIA
39-41
disease,
or propafenone is recommended for cardioversion of
39-41 oral ecainide
recommended.
recommended.
36-38
recent-onset AF.
Digoxin (Level
of Evidence A), verapamil, sotalol, metoprolol (Level of Evidence
Digoxin (Level of Evidence A), verapamil, sotalol, metoprolol (Level of Evidence
IIIABC
Digoxin
of
Evidence
A),
verapamil,
(Level
ofin
Evidence
B),
other(Level
-blocking
agents
(Level
of
Evidence
C)metoprolol
are
converting
InB),
patients
with
recent-onset
AF
andsotalol,
structural
heart
disease,
i.v.inamiodarone
is
IIIABC
other
-blocking
agents
(Level
of
Evidence
C) ineffective
are
ineffective
converting
IA
39-41
recommended.
B), other
-blocking
agents
ofare
Evidence
C)recommended.
are ineffective in converting
recentonset
AF toonset
sinus
rhythm
notare
recommended.
recentAF
to (Level
sinusand
rhythm
and
not
recent- onset AF to sinus rhythm and are not recommended.
(Level
of Evidence
A), verapamil,
sotalol,
(Level of Evidence
patients
with
a life-threatening
deterioration
in haemodynamic
stability
Inwith
patientsDigoxin
a life-threatening
deterioration
in metoprolol
haemodynamic
stability
In IC
IC
IIIABC
B),following
other -blocking
(Level
of Evidence
arecardioversion
ineffective in should
converting
onsetagents
of AF,
emergency
electrical
be
with
a the
life-threatening
deterioration
inC)cardioversion
haemodynamic
stability
In patientsthe
following
onset
of
AF, emergency
electrical
should
be
recentonsetirrespective
AF to sinusof
rhythm
and areofnot
performed,
the duration
therecommended.
AF.
following the
onset ofof the
AF, duration
emergency
cardioversion should be
performed,
irrespective
of the electrical
AF.
performed,Inirrespective
of the
of the deterioration
AF.
patients
with
a duration
life-threatening
in haemodynamic stability
5.1.2.1
Pill-in-the-pocket
approach
IC
5.1.2.1 Pill-in-the-pocket
approach
following the onset
of AF, emergency electrical cardioversion should be
42
performed,
irrespective
ofapproach
the duration
of theto
AF.outpatient administration of oral
refers
The pill-in-the-pocket
5.1.2.1 Pill-in-the-pocket
approach
42 or propafenone (450 to 600 mg) to carefully selected
ecainide (200
to 300 mg)
refers to outpatient administration of oral
The pill-in-the-pocket
approach
42
patients
whose
initial therapy
in hospital
and well tolerated.
5.1.2.1
approach
refers
to outpatient
of oral
The pill-in-the-pocket
approach
ecainide
(200
to Pill-in-the-pocket
300
mg)
or
propafenone
(450
to was
600effective
mg)administration
to carefully
selected
ecainidewhose
(200
to
300
mg)
or
propafenone
to
600
mg)
to
carefully
selected
patients
initial
therapy
in
hospital
was
effective
and
well
tolerated.
42 (450
This
approach
could
be
considered
in
appropriately
selected
patients
who
of have
oral
The pill-in-the-pocket approach refers to outpatient administration
IIaB
patients whose
initial
insymptoms
hospital
effective
andtowell
tolerated.
infrequent
buttherapy
prolonged
ofwas
paroxysmal
AF (PAF).
ecainide
(200
to
300 mg)
or
propafenone
(450
to 600
mg)
carefully
selected
This
approach
could
be
considered
in
appropriately
selected
patients
who
have
patients
whose
initial
therapy
in
hospital
was
effective
and
well
tolerated.
Keypoints
There
is anbe
uncommon
probability
of AF reverting
to AFL with
this approach
and
This
approach
could
considered
appropriately
patients
who have
infrequent
but
prolonged
symptoms
ofinparoxysmal
AFselected
(PAF).
before
antiarrhythmic
medication
initiated,
a selected
beta-blocker,
diltiazem
or
This
approach
could
be considered
inisappropriately
patients
who have
infrequent
but
prolonged
symptoms
of paroxysmal
AF (PAF).
IIaB
IIaB
verapamil
should
be
given
to
prevent
rapid
AV
conduction.
but prolonged
symptoms
of paroxysmal
AF (PAF).
There is aninfrequent
uncommon
probability
of AF reverting
to AFL
with this approach and
There isantiarrhythmic
an uncommon
probability
ofbelow
reverting
with
thisanapproach
and
before
medication
isAFinitiated,
ato AFL
beta-blocker,
diltiazem
or
Patients
the
conditions
areAF
contraindicated
for such
approach:
There
is anwith
uncommon
probability
of
reverting to AFL
with this
approach and
before antiarrhythmic
medication
israpid
initiated,
a beta-blocker,
verapamil
should
be
given
tomore
prevent
AVinitiated,
conduction.
x Those
aged
than 75
years,
before
antiarrhythmic
medication
is
a beta-blocker,diltiazem
diltiazem or
or
verapamil should
beshould
given
to
prevent
rapid AV
x Those
withbe
AFgiven
duration
greater
thanconduction.
7AV
days,
verapamil
to prevent
rapid
conduction.
x
NYHA
Class
III
to
IV
or
signs
of
heart
failure
on
examination,
Patients with the conditions below are contraindicated for such an approach:
withthe
a mean
rate
than 70for
bpm,
Patients
with
conditions
below
are less
contraindicated
for such
approach:
Patients
with
thex AF
conditions
below
are
contraindicated
such
an an
approach:
x Those
aged
more
than
75ventricular
years,
Previous
myocardial
infarction
angina,
x xThose
aged
more
than
75
years,
aged
more
than
75
years,
x Those with
AF
duration
greater
than
7 or
days,
Valvular
disease,greater than 7 days,
x xThose
withheart
AF duration
Those with
AF
greater
days, on examination,
x NYHA
Class
IIIduration
to IV or signs
of than
heart7failure
Cardiomyopathy,
x xNYHA
Class III to IV or signs of heart failure on examination,
NYHA
III
to
IV
or
signs
of less
heartthan
failure on
examination,
x AF
withClass
ax mean
ventricular
rate
bpm,
xAF
Bundle
block,
with abranch
mean ventricular
rate less 70
than
70 bpm,
AF with axmyocardial
mean
ventricular
rate
than
70 bpm,
x Previous
infarction
orless
angina,
xPrevious
Known
sick
sinus syndrome,
myocardial
infarction
or angina,
x Previous
myocardial
infarction
Valvular xheart
disease,
Valvular
heart
disease, or angina,
Valvular xheart
disease,
Cardiomyopathy,
x Cardiomyopathy,
x Bundle
branch block,
Cardiomyopathy,
x Bundle
branch
block,
x Known
sick
sinus syndrome,
Bundle sick
branch
block,
x Known
sinus
syndrome,
x
Low
serum
potassium,
x Known sick sinus syndrome,
x Or renal or hepatic insufficiency.
IIaB
IIaB
22
IaB
IaB
IaB
IaB
Pre-treatment
with amiodarone,
ecainide,
propafenone
or or
sotalol
should
Pre-treatment
with amiodarone,
ecainide,
propafenone
sotalol
should be
be
44-46
IIaB
44-46
considered
to enhance
of DCCV
and prevent
recurrent
AF.AF.
IIaB
considered
to success
enhance success
of DCCV
and prevent
recurrent
IbC
Repeated
DCCV
may
be considered
in highly
symptomatic
patients
refractory
Repeated
DCCV
may be considered
in highly
symptomatic
patients
refractory to
to
IIbC
IIbC
other therapy.
other therapy.
IbC
Pre-treatment
with -blockers,
diltiazem
or verapamil
consideredfor
forrate
rate
Pre-treatment
with -blockers,
diltiazem
or verapamil
maymay
be be
considered
IIbC
IIbC
control,the
although
the of
efficacy
these agents
in enhancing
success
DCCVor
or
control, although
efficacy
theseofagents
in enhancing
success
of ofDCCV
preventing
early recurrence
AF is uncertain.
preventing early
recurrence
of AF isofuncertain.
IIC
IB
IIIC
IIIC
25
26
concluded
factors
in AF,2 score and
Table
11: CHADS
and stroke
rate
interval)
523
4.0 (3.1-5.1)
The various stroke clinical risk factors has led to publication of various stroke
CHADS
schemes.51,52
2 score and as
3 The simplest risk assessment
(4.6-7.3)
337 scheme is the 5.9
shown in Table 11, has good stroke correlation. The CHADS2 [cardiac failure,
hypertension, age, diabetes, stroke (doubled)] risk index evolved from the AF
(6.3-11.1)
220
Investigators4 and Stroke Prevention
in Atrial Fibrillation8.5
(SPAF)
Investigators
criteria, and is based on a point system in which 2 points are assigned for a
history of stroke
years, a history
5 or TIA and 1 point each
12.5>75
(8.2-17.5)
65 is assigned for age
of hypertension, diabetes, or recent cardiac failure.51
used (10.5-27.4)
as an initial, rapid,
The CHADS62 stroke risk stratication 5scheme should be 18.2
and easy-to-remember means of assessing stroke risk. In patients with a
CHADS2 score 2, chronic OAC therapy with a VKA is recommended in a dosea
The adjusted
stroke rateto
was
derived from
the multivariablenormalized
analysis assuming
aspirin
usage;of
these
adjusted
approach
achieve
an international
rationo
(INR)
target
2.5
stroke rates are based on data from a cohort of hospitalized
AF patients, published in 2001, with low
6,52
(range,
2.0
3.0),
unless
contraindicated.
numbers in those with a CHADS2 score of 5 and 6 to allow an accurate judgement of the risk in these
patients. Given that stroke rates are declining overall, actual stroke rates in contemporary non51
hospitalized cohorts may also vary from these estimates. Adapted from Gage F et al. AF = atrial
<<TableCHADS
11>>2 = cardiac failure, hypertension, age, diabetes, stroke (doubled).
fibrillation;
The risk may be calculated based on a point system in which 2 points are
allocated for each Major risk factors; and 1 point each is assigned for
Clinically relevant non major risk factors (see Table 11 on page 27).
6.2 STRATEGIES FOR THROMBOEMBOLIC PROPHYLAXIS
The CHADS2 stroke risk stratication scheme should be used as a simple initial
(and easily remembered) means of assessing stroke risk, particularly suited to
primary care doctors and non-specialists.
In patients with a CHADS2 score of 2, chronic OAC therapy, e.g. with a VKA, is
recommended in a dose adjusted to achieve an INR value in the range of 2.0
3.0, unless contraindicated.
In patients with a CHADS2 score of 0 1, or where a more detailed stroke risk
assessment is indicated, it is recommended to use a more comprehensive risk
factor-based approach incorporating other risk factors for thrombo-embolism (see
Table 12 and Figure 7).56-58
In all cases where OAC is considered, a discussion of the pros and cons with the
patient, and an evaluation of the risk of bleeding complications, ability to safely
sustain adjusted chronic anticoagulation, and patient preferences are necessary.
In some patients, for example, women aged less than 65 years with no other risk
factors (i.e. a CHA2DS2VASC score of 1) aspirin rather than OAC therapy may be
considered.
<<Table 12>>
<<Figure 7>>
28
Table 12. CHA2DS2VASC Score, stroke rate and approach to thromboprophylaxis in patients with AF
Risk factor
Score
Patients (n=7329)
0
1
2
3
4
5
6
7
8
9
1
422
1230
1730
1718
1159
679
294
82
14
0%
1.30%
2.20%
3.20%
4.00%
6.70%
9.80%
9.60%
6.70%
15.20%
CHA2DS2-VASC
score
Recommended
antithrombotic therapy
OAC
No risk factors
29
CHADS2 score 2
No
+
+
Yes
No
CHADS2 Score
Risk Factors
Congestive heart failure
Hypertension
Age 75
Diabetes
Stroke/TIA
Score
1
1
1
1
2
Yes
Yes
No
OAC
Yes
No
Figure 7 Clinical flowchart for the use of oral anticoagulant for stroke prevention in AF. AF = atrial fibrillation; OAC = oral
anticoagulant; TIA = transient ischaemic attack.
7 Clinical flowchart for the use of oral anticoagulant for stroke prevention in AF. AF = atrial fibrillation; OAC = oral anticoagulant; TIA = transient ischaemic attack. A full
ption of theAdapted
CHADS2 from
can bethe
found
on page
?
ESC
Guidelines
for the Management of Atrial Fibrillation (2010 Version) (European heart Journal
2010; doi:10.1093/eurheartj/ehq278)
30
55
VKAtrials,
(international
normalized
ratio prevention,
[INR] 2-3)
In a meta-analysis
There were adjusted-dose
6 large randomized
both primary
and secondary
showed athat
significant
risk reduction
ofevidence
stroke and
risktherapy
reduction
provided 64%
an extensive
and robust
base26%
for VKA
in AF.of all
53,59-63
cause mortality in patients with non valvular AF.
showed a significant
64%was
risk reduction
of stroke 53,59-63
and 26%
risk reduction
of all
Risk of intracranial
hemorrhage
small (0.3-1.8%).
When
VKA is given
mortality
in patients
non valvular
AF.53,59-63
to elderlycause
patients
with
atrial with
fibrillation,
hypertension
must be managed
aggressively.
53,59-63
Risk of intracranial hemorrhage was small (0.3-1.8%).
When VKA is given
to elderly patients with atrial fibrillation, hypertension must be managed
IC
IIaA
Keypoints
Antithrombotic
therapy is recommended for patients with atrial utter as for those
aggressively.
with AF.
IC
IC
Antithrombotic therapy is recommended for patients with atrial utter as for those
with AF.
The selection
of antithrombotic therapy should be considered using the same
criteria irrespective of the pattern of AF (i.e. paroxysmal, persistent, or
The
selection of antithrombotic therapy should be considered using the same
49,50
permanent).
IIaA
IIaA
criteria irrespective of the pattern of AF (i.e. paroxysmal, persistent, or
permanent).49,50
IA
IA
IA
IA
IA
2, chronic
OAC therapy with a VKA is
ForIA
the patients
with a CHADS2 score2 ofregimen
recommended in a dose-adjusted
to achieve an INR range of 2.03.0
49,50,55
recommended
a dose-adjusted
regimen
to achieve an INR range of 2.03.0
(targetin
2.5),
unless contraindicated.
49,50,55
(target 2.5), unless contraindicated.
IA
IA
IA
IA
Patients with 1 major or > 2 clinically relevant non-major risk factors are high
risk, and OAC therapy is recommended, unless contraindicated.53
IA
CHADS
01), a risk factor-based
is recommended,
2 scores
For a more
detailed
or comprehensive
strokeapproach
risk assessment
in AF considering
(e.g. with
major and
clinically
non-major
stroke is
riskrecommended,
factors.53
CHADS2 scores
01),
a risk relevant
factor-based
approach
considering
53
major and clinically relevant non-major stroke risk factors.
IA
Patients with 1 major or > 2 clinically relevant non-major risk factors are high
53
risk, and OAC
therapy
is recommended,
contraindicated.
Patients
with one
clinically relevantunless
non-major
risk factor are at intermediate risk
and antithrombotic therapy is recommended, either as:
IA
IA
i. VKA therapy53 or
IB
IB
IB
IB
IIaA
Patients with no risk factors are at low risk (essentially patients aged <65 years
with lone AF, with none of the risk factors) and the use of either aspirin 75325
mg daily or no antithrombotic therapy is recommended.53
Most patients with one clinically
31 relevant non-major risk factor should be
considered for OAC therapy (e.g. with a VKA) rather than aspirin, based upon an
assessment of the risk of bleeding complications, the ability to safely sustain
IA
IB
IA
or
VKA therapy therapy
andi.antithrombotic
is recommended, either as:
ii. aspirin 75325 mg daily50
i. VKA therapy53 or
IB
IB
patients with is
non-valvular
it isINR
recommended
thatfrom
the target
intensity
of
TheIA
level ofFor
anticoagulation
expressed AF,
as the
and is derived
the ratio
between
anticoagulation
VKA
to maintain
anserum.
INR range of 2.0-3.0 (target
the actual prothrombin
timewith
and athat
of ashould
standardized
control
Keypoints
49,50,64
Patients
with one clinically relevant non-major risk factor are at intermediate risk
2.5)
and
therapy is recommended,
either as: that the target intensity of
Forantithrombotic
patients with non-valvular
AF, it is recommended
For patients withwith
AF awho
have
mechanical
heartan
valves,
it is recommended
that
anticoagulation
VKA
should
to maintain
INR range
of 2.0-3.0 (target
49,50,64 intensity of anticoagulation with a VKA should be based on the type
the target
IB
2.5)
53
IA
i. VKA
therapy
and
position
of theorprosthesis, maintaining an INR of at least 2.5 in the mitral
position
and at
least
an aortic
valve.64,66
For
patients
with
AF 2.0
whoforhave
mechanical
heart valves, it is recommended that
IB
IB
ii.
aspirin
75325
mganticoagulation
daily50
the target intensity of
with a VKA should be based on the type
IB
<<Figure
8>>
and position of the prosthesis, maintaining an INR of at least 2.5 in the mitral
position and at least 2.0 for an aortic valve.64,66
Patients with no risk factors are at low risk (essentially patients aged <65 years
IB
Figure 8:
8: Adjusted
Adjusted
odds
ratios
for
ischaemic
stroke
and
intracranial
bleeding
in relation
relation
to intensity
intensity
of
A target
INR
of 2.5
(target
range
2.0 intracranial
to and
3.0) the
is safe
prevention
in
with
lone
AF,
with
none
of the
riskoffactors)
usefor
of primary
either
aspirin
75325
<<Figure
8>>
Figure
odds
ratios
for
ischaemic
stroke
and
bleeding
in
to
of
53 67 atrial fibrillation.
anticoagulation
in
randomised
trials
of
for
IA
older
more
than
75 years,
unless
contraindicated.
mg
daily
or no antithrombotic
therapy
istherapy
recommended.
anticoagulation
in patients
randomised
trials
of antithrombotic
antithrombotic
therapy
for people
people with
with atrial fibrillation.
IA
IA
Figure 8: Adjusted odds ratios for ischaemic stroke and intracranial bleeding in relation to intensity of
anticoagulation
inmajor
randomised
trials
of antithrombotic
therapy
for
people
atrial
fibrillation.
The
bleeding
rate
for
5 randomized
trials
was
1.2%
per
year. Inbe
2
A target
INR
ofwith
2.5
(target
range
ofrelevant
2.0
to clinical
3.0)
is
safe with
for
primary
prevention
in
Most
patients
one
clinically
non-major
risk
factor
should
IIaAIA
IA
time-dependent
INR
of
in 67
elderlybased
AF upon
cohorts,
older patients
more
thananalyses
75 years,
unless
contraindicated.
considered
for OAC
therapy
(e.g. with
aanticoagulation
VKA)
rather than
aspirin,
an
intracranial bleed
with INRcomplications,
values over 3.5
4.0, and
there was
no
assessment
of theincreased
risk of bleeding
thetoability
to safely
sustain
49,50
The major
bleeding
rate for 5 randomized
trials was 1.2% per year. In 2
adjusted
chronic
anticoagulation,
and patientclinical
preferences.
time-dependent INR analyses of anticoagulation in elderly AF cohorts,
intracranial bleed
increased
with INR
values overfor
3.5patients
to 4.0, and
Anticoagulation
with
VKA is also
recommended
with there
more was
thanno1
moderate risk factor (female gender, age between 65-74, hypertension, diabetes
mellitus, vascular disease, HF, or impaired LV systolic function [ejection fraction
35% or less or fractional shortening less than 25%]).3,4,65
IB
For patients with non-valvular AF, it is recommended that the target intensity of
anticoagulation with a VKA should to maintain an INR range of 2.0-3.0 (target
2.5) 49,50,64
For patients with AF who have mechanical heart valves, it is recommended that
the target intensity of anticoagulation with a VKA should be based on the type
and position of the prosthesis, maintaining an INR of at least 2.5 in the mitral
position and at least 2.0 for an aortic valve.64,66
Reproduced
Reproduced with
with permission
permission from
from Ann
Ann Intern
Intern Med.
Med. Hylek
Hylek E,
E, Singer
Singer D.
D. Risk
Risk factors
factors for
for intracranial
intracranial
hemorrhage
in
<<Figure
8>> taking
hemorrhage
in outpatients
outpatients
taking warfarin.
warfarin. Ann
Ann Intern
Intern Med
Med 1994;120:897-902.
1994;120:897-902.
Reproduced with permission from Ann Intern Med. Hylek E, Singer D. Risk factors for intracranial
hemorrhage in outpatients taking warfarin. Ann Intern Med 1994;120:897-902.
IA
IA
A target INR of 2.5 (target range of 2.0 to 3.0) is safe for primary prevention in
older patients more than 75 years, unless contraindicated.67
The major bleeding rate for 5 randomized clinical trials was 1.2% per year. In 2
time-dependent INR analyses of anticoagulation in elderly AF cohorts,
32 values over 3.5 to 4.0, and there was no
intracranial bleed increased with INR
IA
A target INR of 2.5 (target range of 2.0 to 3.0) is safe for primary prevention in
older patients more than 75 years, unless contraindicated.67
The major bleeding rate for 5 randomized clinical trials was 1.2% per year. In 2
time-dependent INR analyses of anticoagulation in elderly AF cohorts,
intracranial bleed increased with INR values over 3.5 to 4.0, and there was no
increment with values between 2.0 and 3.0 compared with lower INR levels. (See
Figure 6, page 24)
For guide of using VKA in daily practice please refer to Appendix C, page 74.
6.3.2.1 Point-of-care
testing
and self-monitoring
of anticoagulation
increment with values
between
2.0 and 3.0 compared
with lower INR levels. (See
increment
with 24)
values between 2.0 and 3.0 compared with lower INR levels. (See
Figure 6, page
Figure 6, page 24)
important,
and the patient
should
in
a named
clinician.
These point-of-care
devices
mayremain
also THROMBIN
becontact
useful with
in INHIBITORS
remote
places
and allow
6.3.3 ANTICOAGULATION
WITH DIRECT
These
may Point-of-care
also be useful
in remote
allow
patientspoint-of-care
easy accessdevices
to testing.
devices
also places
require and
adequate
patients
easy access
to testing. Point-of-care devices also require adequate
quality assurance
and calibration.
Dabigatran
etexilate
is and
an calibration.
oral prodrug that is rapidly converted by a serum
quality
assurance
esterase6.3.3
to dabigatran,
a potent, WITH
direct,DIRECT
competitive
inhibitor
of thrombin. It does
ANTICOAGULATION
THROMBIN
INHIBITORS
6.3.3
ANTICOAGULATION
DIRECT
INHIBITORS
not require
regular
monitoring andWITH
has a
serumTHROMBIN
half-life of 12
to 17 hours.
Dabigatran etexilate is an oral prodrug that is rapidly converted by a serum
Dabigatran
etexilate is aanpotent,
prodrug
that is rapidly
converted
by a. Itserum
does
esterase to dabigatran,
direct, competitive
inhibitor
of
thrombin
The Randomized
Evaluation of oral
Long-term
Anticoagulation
Therapy
(RE-LY)
. It does
esterase
to regular
dabigatran,
a potent,
direct,
inhibitor
of 17
thrombin
not require
monitoring
and
hasfixed
a competitive
serum
half-life
of
12 to
hours.
was a randomized
trial
comparing
two
doses
of
dabigatran,
given in a
not require regular monitoring and has a serum half-life of 12 to 17 hours.
blinded manner, with open-label use of VKA in patients with atrial fibrillation.58
The Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY)
Dabigatran
110
mg b.i.d. was non-inferior
to VKA for the prevention
of
stroke
The
Randomized
of Long-term
Therapygiven
(RE-LY)
was a
randomizedEvaluation
trial comparing
two fixedAnticoagulation
doses of dabigatran,
in a
and systemic
with
lower rates
offixed
major
bleeding,
whilst dabigatran
was
a embolism
randomized
comparing
of dabigatran,
given in 58
a
blinded
manner, withtrial
open-label
usetwo
of VKA
indoses
patients
with atrial fibrillation.
58
blinded
withb.i.d.
open-label
uselower
of VKA
in
patients
with
atrial
fibrillation.
150 mgDabigatran
b.i.d. manner,
was
of the
stroke
and
systemic
110 associated
mg
waswith
non-inferior
torates
VKA
for
prevention
of
stroke
Dabigatran
110
mg
b.i.d.
was
non-inferior
to
VKA
for
the
prevention
of
stroke
embolism
with
similarembolism
rates of with
major
haemorrhage,
compared
and
systemic
lower
rates of major
bleeding, with
whilstVKA.
dabigatran
and
with lowerwith
rates
of major
whilst
150 systemic
mg b.i.d.embolism
was associated
lower
ratesbleeding,
of stroke
anddabigatran
systemic
150
mg b.i.d.
was associated
with
lower ratescompared
of strokewith
and
systemic
embolism
with similar
rates of major
haemorrhage,
VKA.
embolism with similar rates of major haemorrhage, compared with VKA.
IB
There is therapy.
currently no evidence to support the use of dabigatran for AF associated
with valve
disease,
prosthetic
valve,toinsupport
pregnancy
and
renal
failure.
There
is currently
no evidence
the use
of chronic
dabigatran
for AF
associated
IB
There
is currently
evidencevalve,
to support
the use of
dabigatran
for AF
associated
with
valve
disease,noprosthetic
in pregnancy
and
chronic renal
failure.
with valve disease, prosthetic valve, in pregnancy and chronic renal failure.
Patients with AF who are indicated for OAC but are unwilling to go on VKA
Patients
with AF who arechronic
indicated
OAC but are therapy
unwillingwith
to go
on VKA
because
of the inconvenience,
oralfor
anticoagulant
dabigatran
IB
Patients
with
AF
who are indicated
for
but are unwilling
to go
on VKA
because
of
the
inconvenience,
chronic
oralOAC
anticoagulant
therapy with
dabigatran
IBIBmg twice
150
daily
may
be considered,
unless
because
of the
inconvenience,
chronic
oral contraindicated.
anticoagulant therapy with dabigatran
150 mg twice daily may be considered, unless contraindicated.
150 mg twice daily may be considered, unless contraindicated.
IC
Where patients
are at are
a higher
risk of
(HAS-BLED
110
Where patients
at a higher
riskbleeding
of bleeding
(HAS-BLEDt3),
t3),dabigatran
dabigatran 110
IC
Where
patients
are
at considered,
a higherunless
riskunless
of contraindicated.
bleeding
(HAS-BLED t3), dabigatran 110
mg
daily
may
bemay
considered,
twice
daily
be
contraindicated.
ICICtwicemg
mg twice daily may be considered, unless contraindicated.
There
was however
an increase
in rate
the rate
of gastrointestinalbleeding
bleeding with
There was
however
an increase
in the
of gastrointestinal
with the
the
There was however an increase in the rate of gastrointestinal bleeding with the
IA
IA
Antithrombotic agent should be chosen based upon the absolute risks of stroke
and bleeding and the relative risk and benefit for a given patient.
33
6.3.4 INVESTIGATIONAL AGENTS
However, infarction
clopidogrel
(75mg death.
daily) 56plus aspirin (75-100 mg daily) conferred a
and vascular
relative risk reduction of 11% compared to aspirin.57
However, clopidogrel (75mg daily) plus aspirin (75-100 mg daily) conferred a
57
risk reduction
compared
to aspirin.
There wasrelative
an increased
riskofof11%
major
bleeding
in patients receiving clopidogrel
plus aspirin
compared
to
patients
receiving
aspirin
alone and was broadly similar
There was an57increased risk of major bleeding in patients receiving clopidogrel
to that seen
VKA.
pluswith
aspirin
compared to patients receiving aspirin alone and was broadly similar
to that seen with VKA.57
IIaB
Keypoints
Combination therapy with aspirin 75100 mg plus clopidogrel 75 mg daily, should
Combination
therapy
with aspirin
clopidogrel
mg daily,refusal
should
be considered
for stroke
prevention
in 75100
patientsmgforplus
whom
there 75
is patient
IIaB
be considered
in patients
for whom
there(e.g.
is patient
refusal
toIIaB
take OAC
therapy orfora stroke
clear prevention
contraindication
to OAC
therapy
inability
to
to take OAC
or a clear contraindication
to OACthere
therapy
inability
to
cope or continue
withtherapy
anticoagulation
monitoring), where
is (e.g.
a low
risk of
cope or continue with anticoagulation monitoring), where there is a low risk of
57
bleeding.
57
bleeding.
IIbC
In some patients
with onewith
clinically
relevant
non-major
riskrisk
factor,
In some patients
one clinically
relevant
non-major
factor,e.g.,
e.g.,female
female
IIbC
IIbC
patients
aged
<65
years
other
risk factors,
aspirin
may
patients
aged
<65with
yearsnowith
no other
risk factors,
aspirin
maybebeconsidered
considered
rather
OAC therapy.
rather than
OACthan
therapy.
IN SPECIAL
CIRCUMSTANCES
6.4 ANTICOAGULATION
IN SPECIAL
CIRCUMSTANCES
6.4 ANTICOAGULATION
6.4.1 PERIOPERATIVE ANTICOAGULATION
Patients with
who are
anticoagulated
will require
temporary
interruption
of
VKA AF
treatment
before
surgery or an invasive
procedure.
Many surgeons
require
VKA treatment
surgery
anINR
invasive
procedure.
surgeons
require
an INRbefore
less than
1.5 or or
even
normalization
beforeMany
undertaking
surgery.
The
riskthan
of clinically
even among
undergoing
an INR less
1.5 or signicant
even INR bleeding,
normalization
beforeoutpatients
undertaking
surgery.minor
The
procedures,
should be
weighed even
against
the riskoutpatients
of stroke andundergoing
thrombo-embolism
risk of clinically
signicant
bleeding,
among
minor
in
an
individual
patient
before
the
administration
of
bridging
anticoagulant
procedures, should be weighed against the risk of stroke and thrombo-embolism
therapy. (see Appendix C.1.9, page 80)
in an individual patient before the administration of bridging anticoagulant
therapy. (see
pagewhich
80) has a half-life of 36 42 h, treatment should
If theAppendix
VKA usedC.1.9,
is warfarin,
be interrupted for about 5 days before surgery (corresponding approximately to
If the VKAve
used
is warfarin,
which has a half-life of 36 42 h, treatment should
half-lives
of warfarin),
be interrupted for about 5 days before surgery (corresponding approximately to
Examples
of procedures with a low risk of bleeding,
ve half-lives
of warfarin),
Dental Surgery Restorative Surgery and Extractions
Examples of xprocedures
with a low risk of bleeding,
o Anticoagulation can be continued with an INR of less than 3.0 and
IIaC
IIaC
IIaC
IIaC
o In mostperiod
people
without mechanical prosthetic heart valves,
is required.
x Major Surgery (Interruption
of Anticoagulation Required)
anticoagulation can be safely discontinued temporarily, without the
xneed
Majorfor
Surgery
(Interruption
of Anticoagulation
Required)
heparin
cover. The
decision is made
on the basis of the
o In most people without mechanical prosthetic heart valves,
risk of thrombosis.
anticoagulation
be safely
discontinued
without
the
o In most can
people
without
mechanical temporarily,
prosthetic heart
valves,
need foranticoagulation
heparin cover.
decision
is madetemporarily,
on the basis
of the
canThe
be safely
discontinued
without
the
In patients with AF who
do
not
have
mechanical
prosthetic
heart
valves
or
those
need for heparin cover. The decision is made on the basis of the
risk of thrombosis.
who are not at high risk
risk offor
thrombo-embolism who are undergoing surgical or
thrombosis.
Keypoints
diagnostic procedures that carry a risk of bleeding, the interruption of OAC (with sub
In patients with AF who do not have mechanical prosthetic heart valves or those
patients with AF for
who
mechanical
prosthetic heart
valves
or those
therapeuticInanticoagulation
updotonot
48 have
h) should
be considered,
without
substituting
who
atarehigh
risk
for risk
thrombo-embolism
whowho
areare
undergoing
surgical or
IIaC
IIaCareasnot
who
notanticoagulation
at high
fortherapy.
thrombo-embolism
undergoing
heparin
bridging
(see Appendix
C.1.9
on pagesurgical
80). or
diagnostic diagnostic
procedures
that carry
risk of
bleeding,
the interruption
of of
OAC
procedures
thatacarry
a risk
of bleeding,
the interruption
OAC(with
(with sub
sub
therapeutictherapeutic
anticoagulation
for up to
should
be considered,
without
anticoagulation
for48
up h)
to 48
h) should
be considered,
withoutsubstituting
substituting
In patients
with
a
mechanical
prosthetic
heart
valve
or
AF
at
high
risk
for
as bridging
anticoagulation
therapy.
Appendix
C.1.9
page80).
80).
heparin asheparin
bridging
anticoagulation
therapy.
(see (see
Appendix
C.1.9
onon
page
thrombo-embolism who are undergoing surgical or diagnostic procedures,
bridging Inanticoagulation
with therapeutic
dosesvalve
of either
LMWH
or
patients
with a mechanical
prosthetic
high
risk for
for
InIIaC
patients with
a mechanical
prosthetic
heartheart
valve or or
AFAFatathigh
risk
IIaC
thrombo-embolism
whotheare
undergoing
surgical or
procedures,
unfractionated
heparin during
temporary
interruption
of diagnostic
OAC therapy
should
thrombo-embolism
who
are
undergoing
surgical
or
diagnostic
procedures,
bridging anticoagulation with therapeutic doses of either LMWH or
be considered.
bridging unfractionated
anticoagulation
of ofeither
LMWH
or
heparinwith
duringtherapeutic
the35
temporarydoses
interruption
OAC therapy
should
unfractionated
heparin during the temporary interruption of OAC therapy should
be considered.
Following surgical procedures, resumption of OAC therapy should be considered
need for heparin cover. The decision is made on the basis of the
riskAF
of who
thrombosis.
In patients with
do not have mechanical prosthetic heart valves or those
who are not at high risk for thrombo-embolism who are undergoing surgical or
In
patientsprocedures
with AF who
not ahave
mechanical
prosthetic
heartofvalves
or those
diagnostic
thatdocarry
risk of
bleeding, the
interruption
OAC (with
sub
who
are not
at high risk for
thrombo-embolism
who
are undergoing
surgical or
therapeutic
anticoagulation
for up
to 48 h) should be
considered,
without substituting
diagnostic
procedures
that
carry
a
risk
of
bleeding,
the
interruption
of
OAC
(with
heparin as bridging anticoagulation therapy. (see Appendix C.1.9 on page 80). sub
therapeutic anticoagulation for up to 48 h) should be considered, without substituting
heparin
as bridging
therapy. (see
C.1.9
In patients
with a anticoagulation
mechanical prosthetic
heartAppendix
valve or
AF on
at page
high 80).
risk for
thrombo-embolism who are undergoing surgical or diagnostic procedures,
In
patients anticoagulation
with a mechanical
heartdoses
valve or
at high
risk for
bridging
with prosthetic
therapeutic
of AF
either
LMWH
or
thrombo-embolism
whoduring
are the
undergoing
or diagnostic
procedures,
unfractionated heparin
temporarysurgical
interruption
of OAC therapy
should
bridging
anticoagulation with therapeutic doses of either LMWH or
be considered.
unfractionated heparin during the temporary interruption of OAC therapy should
be
considered.
Following
surgical procedures, resumption of OAC therapy should be considered
at the usual maintenance dose (without a loading dose) on the evening of (or
Following
surgicalafter)
procedures,
of OAC
therapy should
be considered
the next morning
surgery,resumption
assuming there
is adequate
haemostasis.
at the usual maintenance dose (without a loading dose) on the evening of (or
the nextsurgical
morningprocedures
after) surgery,
assuming
there is
haemostasis.
When
require
interruption
ofadequate
OAC therapy
for longer than
48h in high-risk patients, unfractionated heparin or subcutaneous LMWH may be
When
surgical
procedures
require
interruption
of
OAC
therapy
for longer than
considered.
48h in high-risk patients, unfractionated heparin or subcutaneous LMWH may be
considered.
6.4.2 ACUTE STROKE
IIaC
IIaC
IIaC
IIaC
IIaB
IIaB
IIaB
IIbC
IIbC
IIbC
6.4.2
STROKE
Keypoints
In allACUTE
patients
with AF who have had an acute stroke, any uncontrolled
IIaC
2 weeks.
In the presence
of a large infarct,
anticoagulationshould
may be be
delayed
after
In thex presence
of haemorrhage,
anticoagulation
withheld
2 weeks.
until an appropriate
time.
x
IIaC
IIaC
x
IIaC
treatment with usual intensity anticoagulation with VKA (INR 2.03.0), raising the
6.4.3 Anticoagulant
and Antiplatelet
Therapy
UseUse
in Patients
With
6.4.3 Anticoagulant
and Antiplatelet
Therapy
in Patients
WithAtrial
Atrial
intensity of the anticoagulation to a maximum target INR of 3.03.5 may be
Fibrillation
Undergoing
Percutaneous
Coronary
Intervention
Fibrillation
Undergoing
Coronary
Intervention
considered,
ratherPercutaneous
than adding an antiplatelet
agent.
There
is of
a lack
of published
evidence
on what
is the
optimalmanagement
management
There is 6.4.3
a lack
published
onTherapy
what
is
optimal
Anticoagulant
andevidence
Antiplatelet
Usethe
in Patients
With Atrial
strategy in anticoagulated patients with nonvalvular atrial fibrillation (AF) who
Undergoing
Percutaneous
Coronary atrial
Intervention
strategy inFibrillation
anticoagulated
patients
with nonvalvular
fibrillation (AF) who
undergo percutaneous coronary intervention (PCI) and, hence, need antiplatelet
undergo percutaneous
coronary intervention (PCI) and, hence, need antiplatelet
therapy.
therapy. There is a lack of published evidence on what is the optimal management
strategyoninconsensus,
anticoagulated
patients strategy
with nonvalvular
fibrillation
who
Based
the post-PCI
should beatrial
tailored
to the (AF)
individual
undergo
percutaneous
intervention
hence,toneed
and
their
riskpost-PCI
of coronary
thromboembolism
and(PCI)
stent
thrombosis
weighed
against
Based on patient
consensus,
the
strategy
should
beand,
tailored
the antiplatelet
individual
therapy
their
risk. risk
of bleeding
while receiving triple
(see Table 13)
patient and
their
of thromboembolism
andtherapy
stent thrombosis
weighed against
their risk of
bleeding
while receiving
triple therapy
13) to the individual
Based
on consensus,
the post-PCI
strategy (see
shouldTable
be tailored
IIaC
Following elective PCI in patients with AF with stable coronary artery disease,
patient and their risk of thromboembolism and stent thrombosis weighed against
BMS should be considered, and drug-eluting stents avoided or strictly limited to
risk ofPCI
bleeding
while receiving
triple
therapy
(see
Table 13)artery disease,
Following their
elective
in patients
with AF
with
stable
coronary
Keypoints
those
clinical and/or
anatomical
situations
(e.g. long
lesions, small vessels,
BMS should
be considered,
drug-eluting
avoided
strictly limited
to
diabetes,
etc.), where and
a signicant
benetstents
is expected
whenor
compared
with BMS.
Following
elective
PCI
in
patients
with
AF
with
stable
coronary
artery disease,
those
IIaC clinical and/or anatomical situations (e.g. long lesions, small vessels,
IIaC
BMS should be considered, and drug-eluting stents avoided or strictly limited to
Following
elective
PCI, triple
therapy
(VKA, aspirin,
clopidogrel) with
should
be
diabetes, etc.),
where
a signicant
benet
is expected
when compared
BMS.
those clinical and/or anatomical situations (e.g. long lesions, small vessels,
IIaC
considered in the short term, followed by more long-term therapy (up to 1 year)
diabetes, etc.), where a signicant benet is expected when compared with BMS.
VKA plus
clopidogrel
75 mg daily
(or, alternatively,
aspirin 75100
mg daily).
Following with
elective
PCI,
triple therapy
(VKA,
aspirin, clopidogrel)
should
be
36 more
considered
in the short
term,
followed
by
long-term
(up to
1 year)
Following
elective
PCI,
triple therapy
(VKA,
aspirin,therapy
clopidogrel)
should
be
Following elective PCI, clopidogrel should be considered in combination with
IIaC
considered
in the short
term,
followed
by more long-term therapy
(up to daily).
1 year)
with VKA plus
daily
(or,
75100
VKA clopidogrel
plus aspirin 75
for mg
a minimum
of alternatively,
1 month after aspirin
implantation
of amg
BMS, but
patient and their risk of thromboembolism and stent thrombosis weighed against
IIaC
Following their
elective
in patients
with AF
with
stable
coronary
risk ofPCI
bleeding
while receiving
triple
therapy
(see
Table 13)artery disease,
BMS should be considered, and drug-eluting stents avoided or strictly limited to
Following
elective
PCI in patients
with AF
withlong
stablelesions,
coronarysmall
artery vessels,
disease,
those
clinical
and/or
anatomical
situations
(e.g.
IIaC
considered, benet
and drug-eluting
stents
avoided
or strictly
limited
to
diabetes, BMS
etc.),should
wherebe
a signicant
is expected
when
compared
with
BMS.
those clinical and/or anatomical situations (e.g. long lesions, small vessels,
IIaC
IIaC
In the acute setting, patients are often given aspirin, clopidogrel, UFH, or LMWH
(e.g. enoxaparin) or bivalirudin and/or a glycoprotein IIb/IIIa inhibitor (GPI). Drugeluting stents should be limited to clinical situations, as described above (see
Table 13). An uninterrupted strategy of OAC is preferred, and radial access
should be used as the rst choice.
For medium to long-term management, triple therapy (VKA, aspirin, and
clopidogrel) should be used in the initial period (3 6 months), or for longer in
selected patients at low bleeding risk. In patients with a high risk of
cardiovascular thrombotic complications [e.g. high Global Registry of Acute
Coronary Events (GRACE) or TIMI risk score], long-term therapy with VKA may
be combined with clopidogrel 75 mg daily (or, alternatively, aspirin 75 100 mg
daily).
Table 13: Antithrombotic
strategies following coronary artery stenting in patients with AF at moderate to high
<<Table
13>>
thrombo-embolic risk (in whom oral anticoagulation therapy is required)
IIaC
Haemorrhagic risk
Clinical
Stent implanted
Anticoagulation regimen
Following
an ACS with or
without PCI
in patients with AF,
triple therapy (VKA,
setting
aspirin,
clopidogrel)
term
Low or intermediate
(e.g should
Elective be considered
Bare-metal in the short
1 month:
triple(36
therapymonths),
of VKA (INRor
HAS-BLED
0-2) patients at low bleeding risk, followed
2.0-2.5) +
75-100mg/day
longer
in score
selected
byaspirin
long-term
therapy
+clopidogrel 75 mg/day
with VKA plus clopidogrel 75 mg daily (or, alternatively,
aspirin 75100 mg daily).
Lifelong: VKA (INR 2.0-3.0) alone
Elective
IIaC
IIbC
Drug-eluting
IIbC
IIbC
Elective
Bare-metalc
In>3)
patients with stable vascular disease (e.g. >1 year, 100mg/day
with no acute
events),
VKA
+clopidogrel
75 mg/day
VKA (INR
2.0-3.0) alone
monotherapy may be considered, and concomitant Lifelong:
antiplatelet
therapy
should
ACS
4 weeks: triple therapy
not be prescribed in the
absence of Bare-metalc
a subsequent cardiovascular
event.of VKA (INR
2.0-2.5) + aspirin 75-100mg/day
+clopidogrel 75 mg/day
(or aspirin 100m/day)
Lifelong: VKA (INR 2.0-3.0) alone
Lifelong:
(INR 2.0-3.0)
alone to
with aspirin plus clopidogrel is recommended, but
in AFVKA
patients
at moderate
High
ElectiveOAC should
Bare-metalc
high risk of stroke,
also be given.
(e.g, HAS-BLED score
>3)
ACS = acute coronary syndrome; AF = atrial fibrillation; INR = international normalized ratio; VKA = vitamin
clopidogrel) should be used in the initial period (3 6 months), or for longer in
K antagonist.
selected
patients
low (PPI)
bleeding
risk.
In patients
with a high risk of
Gastric protection
with a proton
pumpatinhibitor
should be
considered
where necessary.
a
cardiovascular
thrombotic complications [e.g. high Global Registry of Acute
Sirolimus, everolimus,
and tacrolimus.
b
CombinationCoronary
of VKA (INR
2.03.0)+aspirin
mg/day
PPI, long-term
if indicated)therapy
may be considered
an
Events
(GRACE)100
or TIMI
risk(with
score],
with VKA as
may
alternative. be combined with clopidogrel 75 mg daily (or, alternatively, aspirin 75 100 mg
c
Drug-eluting stents should be avoided as far as possible, but, if used, consideration of more prolonged (36
daily).
months) triple antithrombotic therapy is necessary.
54
Adapted from Lip et al.
<<Table 13>>
Keypoints
IIaC
IIaC
Following an ACS with or without PCI in patients with AF, triple therapy (VKA,
aspirin, clopidogrel) should be considered in the short term (36 months), or
longer in selected patients at low bleeding risk, followed by long-term therapy
with VKA plus clopidogrel 75 mg daily (or, alternatively, aspirin 75100 mg daily).
IIaC
IIaC
IIbC
IIbC
IIbC
IIbC
IIbC
IIbC
In patients with stable vascular disease (e.g. >1 year, with no acute events), VKA
monotherapy may be considered, and concomitant antiplatelet therapy should
not be prescribed in the absence of a subsequent cardiovascular event.
6.4.5
6.4.5 CARDIOVERSION
CARDIOVERSION
Conversion
transient mechanical
mechanical dysfunction
dysfunction of
of
Conversion of
of AF
AF to
to 70sinus
sinus rhythm
rhythm results
results in
in transient
70
the
and
LAA
("stunning"),
which can
the LA
LA 6.4.5
and CARDIOVERSION
LAA
("stunning"),
can occur
occur after
after spontaneous,
spontaneous,
48,71
71-73 which
48,71 or electrical71-73 conversion of AF. Thrombus may form
pharmacological,
of AF.mechanical
Thrombusdysfunction
may form
pharmacological,
transient
of
Conversionofofor
AFelectrical
to sinus
rhythmconversion
results in after
during
and
the return
of mechanical
during the
thetheperiod
period
of stunning
stunning
and is
is expelled
expelled
return
mechanical
LA and
LAA70 ("stunning"),
which after
can the
occur
afterof spontaneous,
of
thromboembolic
events
during
the
first
10
d
function,
explaining
the
clustering
48,71
71-73
of thromboembolic
the first
d
function, explaining
the clustering
or electrical
conversionevents
of AF. during
Thrombus
may 10
form
pharmacological,
74,75
after
mechanical
may
delayed,
during the 74,75
periodRecovery
of stunningof
is expelled function
after the
return
of mechanical
after cardioversion.
cardioversion.
Recovery
ofand
mechanical
function
may be
be
delayed,
76,46,87
76,46,87
depending
partially
on
the
duration
of
AF
before
conversion.
thromboembolic
events during the first 10 d
the clustering
dependingfunction,
partiallyexplaining
on the duration
of AFofbefore
conversion.
after cardioversion.74,75 Recovery of mechanical function may be delayed,
77,78
76,46,87
partially on the
duration
of AF before
The
thromboembolism
after
cardioversion
is
between
1% and
and 5%
5%77,78 and
and
The risk
risk of
ofdepending
thromboembolism
after
cardioversion
is conversion.
between 1%
is reduced
reduced when
anticoagulation
(INR
2.0
to
3.0)
is
given
for
4
wk
before
and
is
when
anticoagulation
(INR
2.0
to
3.0)
is
given
for
4
wk
before
77,78and
79,80
1%
and
5%
and
The
risk
of
thromboembolism
after
cardioversion
is
between
(see Figure
Figure 9).
9).
after conversion
conversion79,80 (see
after
is reduced when anticoagulation (INR 2.0 to 3.0) is given for 4 wk before and
79,80
For
with AF
requiring
immediate/emergency
cardioversion
because of
For patients
patients
AF with
requiring
immediate/emergency
cardioversion
For with
patients
AF requiring
immediate/emergency
cardioversionbecause
because of
of
haemodynamic
instability,
heparin
(i.v.
bolus
followed
by
infusion,
or weightICIC
haemodynamic
instability,
heparinheparin
(i.v. UFH
UFH
bolusbolus
followed
by by
infusion,
haemodynamic
instability,
(i.v. UFH
followed
infusion,ororweightweightadjusted
therapeutic
dose
LMWH)
is
recommended.
adjusted therapeutic
dose LMWH)
is recommended.
adjusted therapeutic
dose LMWH)
is recommended.
After
cardioversion
in
with
AF
of
48
After immediate/emergency
cardioversion
in patients
hourduration
duration
After immediate/emergency
immediate/emergency
cardioversion
in patients
patients
withwith
AFAF
of of
4848hour
hour
duration
the duration
is unknown,
therapy
recommended
orI IB
longer, or
or
when
the
duration
of
is
unknown,
OAC
therapy
is
recommended
B
or
longer,
orlonger,
when or
thewhen
duration
of AF
AF of
is AF
unknown,
OACOAC
therapy
is is
recommended
6464
for
at
least
4
weeks,
similar
to
patients
undergoing
elective
cardioversion.
64
for at
at least
least 4
4 weeks,
weeks, similar
similar to
to patients
patients undergoing
undergoing elective
elective cardioversion.
cardioversion.
for
AF duration
that38is clearly
<48
h and no
thrombo-embolic risk
risk
Forwith
patients
AF with
duration
that is
<48
h
For
patients
with i.v.
AF
duration
is clearly
clearly
<48 therapeutic
h and
and no
no thrombo-embolic
thrombo-embolic
For
factors,
heparin orthat
weightadjusted
dose LMWH mayrisk
be
IIbCpatients
factors,
i.v. heparin or weight- adjusted therapeutic dose LMWH may be
IC
IB
IIbC
IIbC
For patients with AF duration that is clearly <48 h and no thrombo-embolic risk
factors, i.v. heparin or weight- adjusted therapeutic dose LMWH may be
considered peri-cardioversion, without the need for post-cardioversion oral
anticoagulation.
It is important to stress that in following cardioversion of all patients at high risk of
AF recurrence or with stroke risk factors, consideration should be given towards
long-term anticoagulation, as thromboembolism may occur during asymptomatic
recurrence of AF.
IIB
B
IIB
B
For patients with AF <48 h and at high risk of stroke, i.v. heparin or weightadjusted therapeutic dose LMWH is recommended peri-cardioversion, followed
by OAC therapy with a VKA (INR 2.03.0) long term.49,55,64
In patients at high risk of stroke, OAC therapy with a VKA (INR 2.03.0) is
recommended to be continued long-term.49,55,64
<<Figure 9>>
Figure 9: Cardioversion of haemodynamically stable AF, the role of TOE-guided cardioversion, and
subsequent anticoagulation strategy. AF = atrial fibrillation; DCC = direct current cardioversion; LA = left
atrium; LAA = left atrial appendage; OAC = oral anticoagulant; SR = sinus rhythm; TOE = transoesophageal
echocardiography.
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart
Journal 2010; doi:10.1093/eurheartj/ehq278)
39
IBIB
x For continuation
patients with no
thrombus, cardioversion
x Thereafter,
of identifiable
oral anticoagulation
(INR 2.0 istoreasonable
3.0) is
IIaB
IIaB
immediately
after
reasonable
for at least
4 anticoagulation.
weeks, as for elective cardioversion.
x Thereafter, continuation of oral anticoagulation (INR 2.0 to 3.0) is
IIaB
x For patients in whom thrombus is identified, oral anticoagulation (INR 2.0 to
IIaB
reasonable for at least 4 weeks, as for elective cardioversion.
IIaB
IIaB
apparently
successful
cardioversion,
because
the
risk
of
thromboembolism
often remains
elevated
in suchthrombus
cases.
For patients undergoing
a TOE-guided
strategy
in whom
is identied,
VKA (INR 2.03.0) is recommended for at least 4 weeks, followed by a repeat
For
patients
undergoing
a
TOE-guided
strategy
in
whom
thrombus
is identied,
ICIC to ensure thrombus resolution.
TOE
VKA (INR 2.03.0) is recommended for at least 4 weeks, followed by a repeat
TOE to ensure thrombus resolution.
41
Letter
Clinical characteristica
Points awarded
1
Hypertension
Stroke
Bleeding
Labile INRS
1 or 2
1 or 2
Maximum 9 points
Hypertension is defined as systolic blood pressure .160 mmHg. Abnormal kidney function is defined
as the presence of chronic dialysis or renal transplantation or serum creatinine 200 mmol/L. Abnormal
liver function is defined as chronic hepatic disease (e.g. cirrhosis) or biochemical evidence of significant
hepatic derangement (e.g. bilirubin .2 x upper limit of normal, in association with aspartate
aminotransferase/alanine
aminotransferase/alkaline
a
Hypertension
blood
pressure
.160 refers
mmHg.toAbnormal
function
is defined
phosphatase
.3 isx defined
upper as
limitsystolic
normal,
etc.).
Bleeding
previous kidney
bleeding
history
and/or
as the presence
chronic e.g.
dialysis
or renal
transplantation
or etc.
serum
creatinine
Abnormal
predisposition
to of
bleeding,
bleeding
diathesis,
anaemia,
Labile
INRs200
refersmmol/L.
to unstable/high
liver function
defined
as chronic range
hepatic(e.g.<60%).
disease (e.g.
cirrhosis) or use
biochemical
of significant
INRs
or poor is
time
in therapeutic
Drugs/alcohol
refers toevidence
concomitant
use of
hepaticsuch
derangement
(e.g.
bilirubin
.2 x upper
limit of normal,
in orassociation
with etc.
aspartate
drugs,
as antiplatelet
agents,
non-steroidal
anti-inflammatory
drugs,
alcohol abuse,
INR =
aminotransferase/alanine
aminotransferase/alkaline
international
normalized ratio.
82
phosphatase
.3 x upper
Adapted
from Pisters
et al. limit normal, etc.). Bleeding refers to previous bleeding history and/or
predisposition to bleeding, e.g. bleeding diathesis, anaemia, etc. Labile INRs refers to unstable/high
INRs or poor time in therapeutic range (e.g.<60%). Drugs/alcohol use refers to concomitant use of
drugs, such<<Table
as antiplatelet
14>>agents, non-steroidal anti-inflammatory drugs, or alcohol abuse, etc. INR =
Keypoints
international normalized ratio.
82
Adapted from Pisters et al.
IIaA
IIaA
IIaB
IIaB
43
First-line
No heart disease
Beta-blockers*
OR
Non-dihydropyridine
Calcium channel
blockers
Hypertension
Beta-blockers*
OR
Non-dihydropyridine
Calcium channel
blockers
Beta-blockers*
Ischaemic heart
disease
Congestive heart
failure
Second-line
Digoxin
Chronic obstructive
pulmonary disease
Less effective or
desirable
Digoxin
(can be rst-line in
people unlikely to be
active)
Non-dihydropyridine
Calcium channel
blockers
Ablation + pacing
Beta-blockers*
(excluding carvedilol,
bisoprolol
and metoprolol)
OR
Diltiazem
Amiodarone
Digoxin
* excluding sotalol
diltiazem or verapamil
as monotherapy (can be used in combination with other rate-control agents)
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal
2010; doi:10.1093/eurheartj/ehq278)
44
Table 16: Oral pharmacological agents for rate control in people with atrial fibrillation/atrial flutter
Drug
Oral
loading
dose
Onset
of action
Commonly used
oral maintenance
doses
Beta-blockers
Atenolol
N/A
2 to 3 hr
25 to 50 mg
Carvedilol
N/A
60 to 90 min
6.25 to 25 mg bd
Metoprolol
N/A
4 to 6 hr
Nadolol
N/A
3 to 4 hr
20 to 80 mg/day
Propanolol
N/A
Adverse effects
Hypotension,
heart block,
bradycardia,
asthma, heart failure
In people with
heart failure,
lower doses may
be advisable
(negative inotropic
effect)
In people with
heart failure,
lower doses may
be advisable
In people with
heart failure,
lower doses may
be advisable
(negative
inotropic effect)
60 to 90 min
80 to 240 mg/day
1 to 4 hr
Hypotension,
heart block,
heart failure
Verapamil
1 to 2 hr
Hypotension,
heart block,
heart failure,
digoxin
interaction
N/A
Comments
Other
Digoxin
0.5 to 1.0
mg
2 hr
0.0625 to 0.375
mg/day
Digoxin toxicity,
heart block,
bradycardia
Amiodarone
400 to 800
mg/day
for 1 week
1 to 3 wk
200 mg/day
Photosensitivity
and other skin
reactions,
pulmonary
toxicity,
polyneuropathy,
gastrointestinal
upset,
bradycardia,
hepatic toxicity,
thyroid
dysfunction,
torsades de
pointes (rare)
First-line therapy
only for people
unlikely to be active
(eg, older people or
infirm) and for
people with heart
failure.
Less effective in
hyperadrenergic
states
Although there
is fairly good
evidence of
efficacy, this is
an agent of last
resort in this
indication, due
to its long-term
toxicity
Keypoints
IB
IB
IC
IC
ICIC
IIbB
IC
IC
In pre-excitation AF, or in patients with a history of AF, preferred drugs for rate
control are propafenone or amiodarone
IIbB
IIbB
IIbB
IIbB
IIa
C
IIaC
IIbC
IIb
C
IIIB
III
B
Digitalis should not be used as the sole agent to control the rate of ventricular
response in patients with paroxysmal AF.88
IB
IB
IIaC
IIaC
Intravenous amiodarone can be useful to control the heart rate in patients with
AF when other measures are unsuccessful or contraindicated. 35
taken of
to avoid
severe
The combination
of digoxin
and -blocker
A combination
digoxin
andbradycardia.
either a -blocker,
diltiazem,
or verapamil
is
Keypoint
morethe
effective
combination
of digoxin
with
a CCB.89in patients
reasonableappears
to control
heartthan
ratethe
both
at rest and
during
exercise
with AF.
A combination of digoxin and either a -blocker, diltiazem, or verapamil is
IIaB
IIaB
reasonable to control the heart rate both at rest and during exercise in patients
<<Figure 11>>
with AF.
<<Figure 11>>
46
Figure 11 : Rate control. COPD = chronic obstructive pulmonary disease. *Small doses of b1-elective
Figure
11may
: Rate
control.
COPDif=rate
chronic
obstructive
pulmonary
*Small doses
of b1-elective
blockers
be used
in COPD
control
is not adequate
with disease.
non-dihydropyridine
calcium
channel
blockers
mayand
be digoxin.
used in COPD
if rateiscontrol
is notforadequate
with in
non-dihydropyridine
calcium
channel
antagonists
Amiodarone
also used
rate control
patients who do not
respond
to
antagonists
and
digoxin.
Amiodarone
is
also
used
for
rate
control
in
patients
who
do
not
respond
glycosides, b-blockers or non-dihydropyridine calcium antagonists. Dronedarone may also be used for rateto
glycosides,
b-blockers
or non-dihydropyridine
calcium
antagonists. Dronedarone may also be used for rate
control in patient
with recurrent
episodes of atrial
fibrillation.
control in patient with recurrent episodes of atrial fibrillation.
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart
Journal 2010; doi:10.1093/eurheartj/ehq278)
including combination of drugs, has failed or rhythm control with drugs and/or LA
ablation hasAblation
failed.of the atrioventricular node is a palliative but irreversible procedure and
is therefore reasonable in patients in whom pharmacological rate control,
permanent
pacemaker implantation.
It is suggested
that programming
the pacemaker initially for the 1 st month postablation to a higher nominal rate (90 beat per minutes) will reducest the risk of
It is suggested that programming the pacemaker initially for the 1 month postsudden cardiac
death.
ablation
to a higher nominal rate (90 beat per minutes) will reduce the risk of
sudden cardiac death.
Keypoints
Ablation of the AV node to control heart rate should be considered when the rate
of thewith
AV node
to control heart rate
should
be considered
the rate
cannot
controlled
pharmacological
agents
and
when AF when
cannot
be
IIaB
IIa B be Ablation
cannot
be controlled
with pharmacological
agents
when AF
cannot
be
prevented by
antiarrhythmic
therapy
or is associated
with and
intolerable
side
effects,
prevented by antiarrhythmic therapy or is associated with intolerable side effects,
and direct catheter-based
or surgical
ablation
of AFofisAF
not
indicated,
has
failed,
or
and
direct
catheter-based
or
surgical
ablation
is
not
indicated,
has
failed,
or
is rejected.90,100
is rejected.90,100
the AV
node should
be considered
for patients
with
permanent AF
AF
Ablation of Ablation
the AVofnode
should
be considered
for patients
with
permanent
IIaB
IIa Ban indication
and an indication
CRT (NYHA
functional
III ambulatory
or ambulatoryclass
class IV
IV
and
for CRTfor(NYHA
functional
classclass
III or
symptoms
despite
optimal
medical
therapy,
LVEF
<35%,
QRS
width
>130
symptoms despite
101-104 optimal medical therapy, LVEF <35%, QRS width >130
101-104 ms).
ms).
Ablation of the AV node should be considered for CRT non-responders in whom
IIaC
Ablation
of AF
theprevents
AV node
shouldbiventricular
be considered
for CRT
in whom
effective
stimulation
and non-responders
amiodarone is ineffective
or
IIa C
AF prevents
effective biventricular stimulation and amiodarone is ineffective or
contraindicated.
contraindicated.
IIaC
In patients with any type of AF and severely depressed LV function (LVEF <35%)
and severe heart failure symptoms (NYHA III or IV), biventricular stimulation
C
with any type of AF and severely depressed LV function (LVEF <35%)
InIIapatients
should be considered after AV node ablation.
and severe heart failure symptoms (NYHA III or IV), biventricular stimulation
should be considered
AV node
node to
ablation.
Ablation of after
the AV
control heart rate may be considered when
IIbC
IIb
C
pharmacological
direct
ablation
AF is not indicated,
Ablation ofcontrolled
the AVwithnode
to controlagents,
heartand
rate
may
be ofconsidered
when
has failed, or is
rejected.
tachycardia-mediated
cardiomyopathy
is suspected and the rate cannot be
IIbC
IIb C
IIb C
In patients with any type of AF, moderately depressed LV function (LVEF <45%)
and mild heart failure symptoms (NYHA II), implantation of a CRT pacemaker
may be considered after AV node ablation.
IIbC
IIb
C
In patients with paroxysmal AF and normal LV function, implantation of a dualchamber (DDDR) pacemaker with mode-switch function may be considered after
AV node ablation.
IIbC
IIb
C
IIIC
Catheter ablation of the AV node should not be attempted without a prior trial of
medication, or catheter ablation for AF, to control the AF and/or ventricular rate in
patients with AF.
IIbC
III C
The term
term rhythm
rhythm control
control encompasses
encompasses the
the processes
processes of
of conversion
conversion of
of atrial
atrial
The
brillation (AF)
(AF) or
or atrial
atrial utter
utter (AFI)
(AFI) to
to normal
normal sinus
sinus rhythm,
rhythm, as
as well
well as
as the
the
brillation
maintenance of
of sinus
sinus rhythm.
rhythm.
maintenance
Maintenance of
of sinus
sinus rhythm
rhythm may
may also
also be
be referred
referred to
to as
as
Maintenance
relapse or
or recurrence,
recurrence, and
and may
may be
be achieved
achieved by
by
relapse
nonpharmacological means,
means, or
or both
both (hybrid
(hybrid therapy).
therapy).
nonpharmacological
prevention of
of AF/AFI
AF/AFI
prevention
pharmacological or
or
pharmacological
In the
the absence
absence of
of spontaneous
spontaneous reversion,
reversion, cardioversion
cardioversion is
is chosen
chosen as
as part
part of
of the
the
In
rhythm-control strategy.
strategy.
rhythm-control
The following
following are
are the
the guiding
guiding principles
principles of
of antiarrhythmic
antiarrhythmic drug
drug therapy
therapy to
to
The
maintain sinus
sinus rhythm
rhythm in
in AF:
AF:
maintain
(1) Treatment
Treatment is
is motivated
motivated by
by attempts
attempts to
to reduce
reduce AF-related
AF-related symptoms.
symptoms.
(1)
(2) Efficacy
Efficacy of
of antiarrhythmic
antiarrhythmic drugs
drugs to
to maintain
maintain sinus
sinus rhythm
rhythm is
is modest.
modest.
(2)
(3) Clinically
Clinically successful
successful antiarrhythmic
antiarrhythmic drug
drug therapy
therapy may
may reduce
reduce rather
rather than
than
(3)
eliminate recurrence
recurrence of
of AF.
AF.
eliminate
(4) If
If one
one antiarrhythmic
antiarrhythmic drug
drug fails,
fails, a
a clinically
clinically acceptable
acceptable response
response may
may be
be
(4)
achieved with
with another
another agent.
agent.
achieved
(5) Drug-induced
Drug-induced proarrhythmia
proarrhythmia or
or extra-cardiac
extra-cardiac side
side effects
effects are
are frequent.
frequent.
(5)
(6) Safety
Safety rather
rather than
than efficacy
efficacy considerations
considerations should
should primarily
primarily guide
guide the
the choice
choice
(6)
of antiarrhythmic
antiarrhythmic agent
agent
of
8.1 EFFICACY
EFFICACY OF
OF ANTIARRHYTHMIC
ANTIARRHYTHMIC DRUGS
DRUGS IN
IN PREVENTING
PREVENTING
8.1
RECURRENT ATRIAL
ATRIAL BRILLATION
BRILLATION
RECURRENT
In a
a recent
recent meta-analysis
meta-analysis of
of 44
44 randomized
randomized controlled
controlled trials
trials comparing
comparing
In
105
the antiarrhymic
antiarrhymic drugs
drugs signicantly
signicantly
antiarrhythmic drugs
drugs against
against control,
control,105
the
antiarrhythmic
reduced the
the rate
rate of
of recurrent
recurrent AF.
AF. Overall,
Overall, the
the likelihood
likelihood of
of maintaining
maintaining sinus
sinus
reduced
106
rhythm is
is approximately
approximately doubled
doubled by
by the
the use
use of
of antiarrhythmic
antiarrhythmic drugs.
drugs.106
rhythm
Amiodarone was
was superior
superior to
to class
class II agents
agents and
and sotalol.
sotalol.
Amiodarone
The number
number of
of patients
patients needed
needed to
to treat
treat for
for 1
1 year
year was
was 2
2
9.
9. Withdrawal
Withdrawal due
due to
to
The
side effects
effects was
was frequent
frequent (1
(1 in
in 9
9
27
27 patients),
patients), and
and all
all drugs
drugs except
except amiodarone
amiodarone
side
105
The number
number of
of
and propafenone
propafenone increased
increased the
the incidence
incidence of
of proarrhythmia.
proarrhythmia.105 The
and
patients needed
needed to
to harm
harm was
was 17
17
119.
119. Most
Most of
of the
the trials
trials included
included in
in the
the analysis
analysis
patients
enrolled relatively healthy patients without severe concomitant cardiac disease.
Although mortality was low in all studies (0 4.4%), rapidly dissociating sodium
channel blockers (disopyramide phosphate, quinidine sulfate) were associated
with increased mortality.
8.2 CHOICE OF ANTIARRHYTHMIC DRUGS
Antiarrhythmic therapy for recurrent AF is recommended on the basis of
choosing safer, although possibly less efficacious, medication before resorting to
more effective but less safe therapy. Upon initiation of antiarrhythmic therapy,
regular ECG monitoring is recommended (see Table 16. page 45).
8.2.1 PATIENTS WITH LONE ATRIAL FIBRILLATION
In patients with no or minimal heart disease, -blockers represent a logical rst
attempt to prevent recurrent AF when the arrhythmia is clearly related to mental or
physical stress (adrenergic AF). Flecainide, propafenone, sotalol, or dronedarone
is usually prescribed as second line agents (Figure 12, page 50).107,108
<<Figure 12>>
49
Individual drugs and their main disadvantages are listed in Table 17.
Individual drugs and their main disadvantages are listed in Table 17.
Amiodarone is the most efficacious antiarrhythmic drug for the prevention of
105,109-111
Amiodarone
the mostseveral
efficacious
antiarrhythmic
drug
for failed
the prevention
have
to identify of
a
recurrent AF.isHowever,
meta-analyses
105,109-111
haveInfailed
to the
identify
a
recurrent AF.
However,
severalon
meta-analyses
benecial
effect
of amiodarone
cardiovascular outcomes.
view of
better
benecial
of amiodarone
on cardiovascular
In view ofas
thethe
better
safety
andeffect
potential
outcome benet,
dronedaroneoutcomes.
may be preferable
rst
safety
and potential
outcome
dronedarone
may be preferable
the rst
antiarrhythmic
option,
at leastbenet,
in patients
with symptomatic
AF and as
underlying
antiarrhythmic option,
at least
in patients
with symptomatic
AF and symptoms,
underlying
cardiovascular
disease.
Should
dronedarone
fail to control
cardiovascular
disease.
Should dronedarone fail to control symptoms,
amiodarone
might
then be necessary.
amiodarone might then be necessary.
Dronedarone can be used safely in patients with ACS, chronic stable angina,
Dronedarone heart
can be
used safely
in patients
with only
ACS,bechronic
stable
angina,
hypertensive
disease.
Dronedarone
should
used in
maintaining
hypertensive
heartin disease.
Dronedarone
should
used inDronedarone
maintaining
sinus
rhythm and
whose normal
heart rhythm
hasonly
beenberestored.
sinus rhythm
normal
has been restored. Dronedarone
should
not beand
usedininwhose
patients
with heart rhythm
failure.112
should not be used in patients with heart failure.112
Figure 13. Choice of antiarrhythmic drug according to underlying pathology. ACEI=angiotensin-converting enzyme inhibitor; ARB=
angiotensin receptor blocker; CAD = coronary artery disease; CHF=congestive heart failure; HT=hypertension; LVH =left ventricular
hypertrophy; NYHA=New York Heart Association; unstable=cardiac decompensation within the prior 4 weeks. Antiarrhythmic agents
are listed in alphabetical order within each treatment box. ? = evidence for upstream therapy for prevention of atrial remodelling still
remains controversial.
Adapted with modification from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal
2010; doi:10.1093/eurheartj/ehq278)
50
x amiodarone21,105,113
IA
x dronedarone85,86
IA
x ecainide105,114
IA
x propafenone105,113
51
sideside
effect
effect
prole.
prole.
TheThe
following
following
antiarrhythmic
antiarrhythmic
drugs
drugs
areare
recommended
recommended
for for
rhythm
rhythm
control
control
in in
patients
patients
withwith
AF,AF,
depending
depending
on on
underlying
underlying
heart
heart
disease:
disease:
Keypoints
x amiodarone21,105,113
IA
I AIA
21,105,113
21,105,113
x amiodarone
x amiodarone
x dronedarone85,86
85,8685,86
x dronedarone
x dronedarone
IA
I AIA
x ecainide105,114 105,114
105,114
x ecainide
x ecainide
I AIA
IA
105,113
105,113
105,113
I AIA
IxApropafenone
x propafenone
x propafenone
21,48,105 21,48,105
21,48,105
IxAd,I-sotalol
I AIA
x d,I-sotalol
x d,I-sotalol
IA/C
I A/C
IB
IB
In patients with severe heart failure, NYHA class III and IV or recently unstable
(decompensation within the prior month) NYHA class II, amiodarone should be
the drug of choice.115
IA
IA
IC
IC
IIa C
IIaC
IIa B
IIaB
IIaC
IIa C
-blockers should be considered for rhythm (plus rate) control in patients with a
rst episode of AF.
III B
IIIB
III C
IIIC
Figure 14. Choice between ablation and antiarrhythmic drug therapy for patients with and without structural heart disease. Proposed integration
of antiarrhythmic drug and catheter ablation for AF in patients with relevant underlying heart disease and for those with no or minimal heart
disease, including hypertension (HT) without left ventricular hypertrophy (LVH). More extensive LA ablation may be needed; *usually PVI is
appropriate. AF= atrial fibrillation; CAD = coronary artery disease; CHF = congestive heart failure; HT=hypertension; LVH=left ventricular
hypertrophy; NYHA=New York Heart Association; PVI=pulmonary vein isolation. Antiarrhythmic agents are listed in alphabetical order within
each treatment box. Please note that left atrium (LA) ablation as first-line therapy (dashed line) is a Class IIb recommendation for patients with
paroxysmal AF and no or minimal heart disease, who remain highly symptomatic, despite rate control, and who reject antiarrhythmic drug
therapy.
<<Figure 14>>
Adapted with modification from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010;
doi:10.1093/eurheartj/ehq278)
IIa A
53
Ablationheart
may disease,
particularlythe
benefit
younger
patients and
with the
lone benet
AF who are
minimal organic
treatment
strategies
risk
frequently symptomatic and for whom long-term antiarrhythmic poses higher risk
ratio of catheter
ablation
are
less
well
established.
Extensive
and
frequently
and lifestyle cost.
repeated ablation procedures may be necessary in these patients, and it seems
reasonableFor
to patients
recommend
that persistent
they should
refractory to
antiarrhythmic
drug
with either
AF orbe
long-standing
persistent
AF, and no
or
minimalablation
organic heart
disease, the
treatment
and the benet risk
treatment before
is considered
(See
Figure strategies
14).
ratio of catheter ablation are less well established. Extensive and frequently
Ablation ofbutcommon
atrial
utter
is but
recommended
as part
of attempts.
an AF ablation
encouraging
success
rates,
very often requires
several
Keypoints
procedure if documented prior to the ablation procedure or occurring during the
18
Ablation of common atrial utter is recommended as part of an AF ablation
AF ablation.
IIB
B
procedure if documented prior to the ablation procedure or occurring during the
AF ablation.18
IIaB
IIa
B
IIaC
IIa
C
IIaB
IIa
B
IIbC
IIb
C
Catheter ablation of AF may be considered in patients with symptomatic longstanding persistent AF refractory to antiarrhythmic drugs.
IIbB
IIb
B
IIbB
IIb
B
Keypoints
Surgical ablation of AF should be considered in patients with symptomatic AF
120,127,128
undergoingSurgical
cardiacablation
surgery.
of AF should be considered in patients with symptomatic AF
IIaA
IIa A
120,127,128
undergoing cardiac surgery.
Minimally invasive
ablationablation
of AF of
without
concomitant
cardiac
is
Minimallysurgical
invasive surgical
AF without
concomitant
cardiacsurgery
surgery is
feasible
may be
in patients
with with
symptomatic
AFAFafter
of
feasible
and performed
may be performed
in patients
symptomatic
afterfailure
failure of
IIbC
IIb C and
catheter ablation.
catheter ablation.
8.3.3 SUPPRESSION OF AF THROUGH PACING
8.3.3 SUPPRESSION
OF AF THROUGH
54 PACING
Several studies have examined the role of atrial pacing to prevent recurrent
IIb C
Surgical ablation
AF may
performed
in patients
with with
asymptomatic
Surgical of
ablation
of AFbe
should
be considered
in patients
symptomatic AF
AF
IIa A
120,127,128
undergoing
cardiac surgery
if feasible
with minimal risk.
undergoing
cardiac surgery.
IIb C
Surgical ablation
AF mayofbeAF
performed
in patients with
asymptomatic
Minimally invasive
surgicalofablation
without concomitant
cardiac
surgeryAF
is
IIb C
undergoing
surgery
feasible with
risk.
feasible and
may becardiac
performed
inifpatients
withminimal
symptomatic
AF after failure of
catheter ablation.
Minimally invasive surgical ablation of AF without concomitant cardiac surgery is
IIb C
8.3.3 SUPPRESSION
OF AF THROUGH PACING
catheter ablation.
8.3.3 SUPPRESSION
OF AF
PACING
Several studies
have examined
theTHROUGH
role of atrial
pacing to prevent recurrent
paroxysmal AF. In patients with symptomatic bradycardia, the risk of AF is lower
Several studies have examined129
the role of atrial pacing to prevent recurrent
with atrial than with ventricular pacing. In patients with sinus node dysfunction
paroxysmal AF. In patients with symptomatic bradycardia, the risk of AF is lower
129 randomized trials support atrial or
frompacing.
several
and normalwith
AVatrial
conduction,
than with data
ventricular
In patients with sinus node
dysfunction
dual-chamber
ventricular
pacing
for prevention
oftrials
AF.130-133
data
from several
randomized
supportPatients
atrial or
and rather
normal than
AV conduction,
with paroxysmal
AF rather
and symptomatic
shouldof be
referred
for
dual-chamber
than ventricular bradycardia
pacing for prevention
AF.130-133
Patients
with paroxysmal
and symptomatic
bradycardia
should be referred for
electrophysiological
review AF
for consideration
of atrial
based pacing.
electrophysiological review for consideration of atrial based pacing.
IIaB
Keypoint
When ventricular
pacing with dual-chamber devices is unavoidable because of
When ventricular pacing with dual-chamber devices is unavoidable because of
IIaB
IIaB
concomitant
disease of
the AV
system,
the the
evidence
is isless
concomitant
disease
of conduction
the AV conduction
system,
evidence
lessclear
clear that
that
pacing ispacing
superior.
Although
atrial-based
pacing
is associated
a
atrial-basedatrial-based
is superior.
Although
atrial-based
pacing
is associatedwith
with a
lowerofburden
of AF
and stroke
risk compared
to ventricular-basedpacing
pacing in
in
lower burden
AF and
stroke
risk compared
to ventricular-based
pacing as
as a
patients requiring
pacemakers
for bradyarrhythmias,
value
ofofpacing
a
patients requiring
pacemakers
for bradyarrhythmias,
the the
value
primaryfor
therapy
for prevention
of recurrent
AF not
has been
not been
proven.
primary therapy
prevention
of recurrent
AF has
proven.
remodelling associated
with inhibitors
hypertension,
heart angiotensin
failure, or
Treatmentsmyocardial
with angiotensin-converting
enzyme
(ACEIs),
inammation (e.g. after cardiac surgery) and therefore may deter the
receptor blockers
(ARBs), aldosterone antagonists, statins, and omega-3
development of new AF (primary prevention) or, once established, its rate of
polyunsaturated
fattyor progression
acids (PUFAs)
are usually
referred
to as 135upstream
recurrence
to permanent
AF (secondary
prevention).
therapies for AF.
Treatments with angiotensin-converting enzyme inhibitors (ACEIs), angiotensin
Primary prevention
8.4.1 ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND
ANGIOTENSIN RECEPTOR BLOCKERS
IIa A
IIa B
signicant
reduction infor
RR prevention
of incident AF.
ACEIs andstatistically
ARBs should
be25%
considered
of138new-onset AF in
Keypoints
patients with heart failure and reduced ejection fraction.136-140
ACEIs and ARBs should be considered for prevention of new-onset AF in
IIaA
IIa
A
patients with heart failure and reduced ejection fraction.136-140
ACEIs and ARBs should be considered for prevention of new-onset AF in
138,141,142
patients with
hypertension,
with left ventricular
hypertrophy.
ACEIs
and ARBs particularly
should be considered
for prevention
of new-onset AF in
IIaB
IIa
B
138,141,142
patients with hypertension, particularly with left ventricular hypertrophy.
III C
Upstream therapies with ACEIs, ARBs, and statins are not recommended for
Upstream therapies with ACEIs, ARBs, and statins are not recommended for
primary
IIIC
III
C prevention of AF in patients without cardiovascular disease.
primary prevention of AF in patients without cardiovascular disease.
Secondary prevention
Secondary prevention
55
Several relatively
small prospective
randomized
controlled
Several relatively
small prospective
randomized
controlled trials
trials have
have
demonstrated
that therapy
ACEI/ARB
conferred
an additional
benet
demonstrated
that with
therapy
with ACEI/ARB
conferred
an additional
beneton
onrisk
risk
artery
bypass
grafting, isolated orFATTY
in combination
with
valvular
interventions.
8.4.4
POLYUNSATURATED
ACIDS
AND
Statins
bebe
considered
of ofnew-onset
AF
inALDOSTERONE
patients
with
should
consideredforforprevention
preventionACIDS
new-onset
AF
after
coronary
148,150
8.4.4 may
POLYUNSATURATED
FATTY
AND
ALDOSTERONE
ANTAGONIST
underlying
heartgrafting,
disease,isolated
particularly
heart
failure.151,152
artery
bypass
or in
combination
with valvular interventions.
ANTAGONIST
148,150
Statins
maythere
be is
considered
prevention
of any
new-onset
AF in patients
At present,
no robust for
evidence
to make
recommendation
for the with
use
IIbB
IIb
B
151,152
8.4.4
POLYUNSATURATED
FATTY
ACIDS
AND prevention
ALDOSTERONE
underlying
heart
disease,
particularly
heart
failure.
At present,
there
is or
no
robust
evidence
to for
make
anyorrecommendation
for ofthe
of
PUFAs
aldosterone
antagonist
primary
secondary
AF.use
ANTAGONIST
Statins
may
be considered
for prevention
of ornew-onset
in patients
with
of PUFAs
or aldosterone
antagonist
for primary
secondaryAF
prevention
of AF.
151,152
8.4.4
POLYUNSATURATED
FATTY
ACIDS
AND
ALDOSTERONE
underlying heart disease, particularly heart failure.
At present,ANTAGONIST
there is no robust evidence to make any recommendation for the use
of
PUFAs
or
aldosterone antagonistFATTY
for
primary
or secondary
prevention
of AF.
8.4.4
POLYUNSATURATED
ACIDS
ALDOSTERONE
At present, there is no robust
evidence to
make any AND
recommendation
for the use
ANTAGONIST
of PUFAs or aldosterone antagonist for primary or secondary prevention of AF.
At present, there is no robust evidence to make any recommendation for the use
of PUFAs or aldosterone antagonist for primary or secondary prevention of AF.
56
may be
performed.
DCCV are
is 95%particularly
successful but useful
pharmacological
Short-actingcardioversion
-blockers
(e.g.
esmolol)
when
cardioversion
is more
was shown
be more
haemodynamic
instability
is a commonly
concern. used.
OtherAmiodarone
atrioventricular
nodalto blocking
effective
than
placebo
in
converting
post-operative
AF
to
sinus
rhythm.
agents, such as non-dihydropyridine calcium channel antagonists, can be used
as alternatives,
but digoxin is less effective when adrenergic tone is high. The
Short-acting -blockers (e.g. esmolol) are particularly useful when
agents usedhaemodynamic
for rate control
of AF following
cardiac
surgery
are listednodal
in Table
15.
instability
is a concern.
Other
atrioventricular
blocking
agents, such as non-dihydropyridine calcium channel antagonists, can be used
A number as
of alternatives,
studies have
increased
stroke intone
patients
but shown
digoxin an
is less
effective risk
whenofadrenergic
is high.after
The
agents used
for rate controlwith
of AFheparin
followingor
cardiac
are listed inwhen
Table AF
15.
cardiac surgery.
Anticoagulation
VKAsurgery
is appropriate
persists longer than 48 h.159 Standard precautions regarding anticoagulation
A number of studies have shown an increased risk of stroke in patients after
pericardioversion
should be used (see Section 4.3).
Keypoints
Oral
-blockers are recommended to prevent post-operative AF for patients
undergoing cardiac surgery in the absence of contraindications.153,154
I AIA
undergoing
cardiac
in the absence ofdrugs
contraindications.
If used, -blockers
(or
othersurgery
oral antiarrhythmic
for AF management) are
154,155
recommended
to
be
continued
until
the
day
of
surgery.
If used, -blockers (or other oral antiarrhythmic drugs for AF management) are
I BIB
B
IIaB
If IIa
sinus
rhythm
is restored
duration
of anticoagulation
be risk
for
a minimum
of 4 successfully,
weeks but more
prolonged
in the presenceshould
of stroke
a minimumfactors.
of 4159weeks but more prolonged in the presence of stroke risk
159
factors.
IIa
C
IIaC
postoperative
AF in an
attemptbe
to maintain
sinus rhythm.
Antiarrhythmic
medications
should
considered
for recurrent or refractory
Sotalol
may
considered
for prevention
of after
AF after
cardiacsurgery,
surgery, but
but is
postoperative
AF considered
in
an be
attempt
to prevention
maintain
sinus
rhythm.
Sotalol
may
be
for
of
AF
cardiac
is
153
IIb
A
IIbA
with risk of proarrhythmia.
associated associated
with risk of
proarrhythmia.153
Biatrial pacing may be considered for prevention of AF after cardiac surgery.153
IIb
A
IIbA
Biatrial
pacing may be considered for prevention of AF after cardiac surgery.153
IIb
B
IIbB
cardiac
surgery,
but are associated
with to
risk.
Corticosteroids
may
be considered
in order
reduce the incidence of AF after
cardiac surgery, but are associated with risk.157
161
Atrial flutter is less common than AF after cardiac surgery,
but
pharmacological therapy is similar. Prevention of postoperative atrial flutter is as
161
Atrial flutter
but
is asless
common
AFoverdrive
after pacing
cardiac
surgery,useful
difficult
prevention
of AF, than
but atrial
is generally
for
pharmacological
therapy
is similar.
Prevention
of postoperative
atrial flutter is as
termination
of atrial
flutter when
epicardial electrodes
are in place.
difficult as prevention of AF, but atrial overdrive pacing is generally useful for
termination of atrial flutter when epicardial electrodes are in place.
9.2 ACUTEAF
CORONARY
SYNDROME
occurs with an
incidence between
2 to 21% in patients with ACS162 and is
58
more commonly associated with ACS in older patients and those with higher
162
Ib B
flutter
is
less
common
than
AF
after
cardiac
surgery,161
but
9.2 ACUTEpharmacological
CORONARY SYNDROME
therapy is similar. Prevention of postoperative atrial flutter is as
difficult as prevention of AF, but atrial overdrive pacing is generally useful for
termination of atrial flutter when epicardial electrodes are in place.
Direct-current
cardioversion is recommended for patients with severe
ACS are based primarily on consensus, because no adequate trials have tested
hemodynamic
compromise
Keypoints alternative
strategies.or intractable ischemia, or when adequate rate
control cannot be achieved with pharmacological agents in patients with ACS
Direct-current cardioversion is recommended for patients with severe
and
AF.
IC
IC
IC
IC
do not haveisLV
dysfunction, bronchospasm,
or AVventricular
block.
Intravenouswho
amiodarone
recommended
to slow a rapid
response to
AF and improve LV function in patients with ACS.
Ia C
Ib C
III B
ventricular response in patients with ACS and AF associated with heart failure.
Administration
of ecainide
or propafenone
is notisrecommended
in in
patients
Administration
of ecainide
or propafenone
not recommended
patientswith
with
III
B
IIIB
AF in the
of ACS.163
AF in the setting
of setting
ACS.163
9.3 WOLFF-PARKINSON-WHITE (WPW) PRE-EXCITATION SYNDROMES
the AV pathways
node, patients
AF are atproperties
risk of rapid
Since accessory
(AP)with
lackovert
the pre-excitation
decrementaland
conduction
of
conduction
across
theovert
AP, resulting
in fast ventricular
the AV node,
patients
with
pre-excitation
and AFrates
areand
at possible
risk ofsudden
rapid
(SCD)
because
degeneration
ventricular
brillation.
This
conductioncardiac
acrossdeath
the AP,
resulting
in of
fast
ventricularinto
rates
and possible
sudden
makes AF in this patient cohort a potentially life-threatening arrhythmia. For
cardiac death
(SCD) because of degeneration into ventricular brillation. This
information relating to acute and long-term pharmacological rate control in
makes AF patients
in thiswith
patient
a potentially
arrhythmia. For
an AP,cohort
see Section
5.1.1, pagelife-threatening
18.
information relating to acute and long-term pharmacological rate control in
patients with
an SUDDEN
AP, see DEATH
SectionAND
5.1.1,
page
18.
9.3.1
RISK
STRATIFICATION
The incidence
SCDRISK
in patients
with the Wolff Parkinson White syndrome
9.3.1 SUDDEN
DEATH of
AND
STRATIFICATION
has ranged from 0.15 to 0.39% over 3- to 22-year follow-up.
The incidence
of SCDofinincreased
patientsrisk
with
The markers
are:the Wolff Parkinson White syndrome
has ranged from
0.15 topre-excited
0.39% over
to 22-year
x Shortest
RR3-interval
<250 follow-up.
ms during spontaneous or induced
AF.
The markers of
increased
risk are: tachycardia.
xA
history of symptomatic
The presenceRR
of multiple
x Shortest xpre-excited
intervalAPs.
<250 ms during spontaneous or induced
59
x Ebsteins anomaly.
AF.
x A history of symptomatic tachycardia.
Immediate SCD.
referral to an experienced ablation centre for catheter ablation is
recommended
for patients
SCD
and have
of ablation
overt AP
Immediate
referral who
to ansurvived
experienced
ablation
centreevidence
for catheter
is
I CIC
conduction.
recommended for patients who survived SCD and have evidence of overt AP
conduction.
Catheter ablation
recommended
in patients
at high
risk risk
of developing
Catheterisablation
is recommended
in patients
at high
of developingAF
AFininthe
the
166
I BIB
presence
ofpresence
an overtofbut
asymptomatic
AP onAP
theonsurface
ECG.
an overt
but asymptomatic
the surface
ECG.166
Asymptomatic
patients
with evidence
an overt
AP should
considered for
for
IIa
B
Asymptomatic
patients with
evidence
of an of
overt
AP should
be be
considered
IIaB
166
catheter
the AP
only
a full explanation
careful
counseling.166
catheter ablation
ofablation
the APofonly
after
a after
full explanation
andand
careful
counseling.
9.4 HYPERTHYROIDISM
9.4 HYPERTHYROIDISM
and elderly
patients.
AF occurs men
in 10%
to 25%
of patients with hyperthyroidism, more commonly in
men and elderly patients.
Ia B
164
surface
ECG. with evidence of an overt AP should be considered for
Asymptomatic
patients
catheter ablation of the AP only after a full explanation and careful counseling.166
IB
IIa B
9.4 HYPERTHYROIDISM
of the
AP only after
explanation and careful
AF occurs catheter
in 10%ablation
to 25%
of patients
witha full
hyperthyroidism,
more counseling.
commonly166in
men and elderly patients.
9.4 HYPERTHYROIDISM
IC
C
II C
IC
IC
Keypoints
In patients Inwith
active
disease,
antithrombotic
therapy
patients
withthyroid
active thyroid
disease,
antithrombotic
therapyis isrecommended
recommended
IIC
C on the presence of other stroke risk factors.
based
based on the presence of other stroke risk factors.
Administration
of a -blocker
is recommended
to control
the
rateofofventricular
ventricular
Administration
of a -blocker
recommended
to control
rate
When
a -blocker
cannot
beis used,
administration
of athenon-dihydropyridine
IIC
C
inwith
patients
with
AF complicating
thyrotoxicosis,
unless
contraindicated.
responsechannel
inresponse
patients
AF (diltiazem
complicating
thyrotoxicosis,
unless
contraindicated.
calcium
antagonist
or verapamil)
is recommended
to control
the ventricular
ratea in-blocker
patientscannot
with AF
thyrotoxicosis.
When
beand
used,
administration of a non-dihydropyridine
IC
IC
calcium channel antagonist (diltiazem or verapamil) is recommended to control
ventricular
rate in patients
with AF itand
If a rhythmthe
control
strategy
is desirable,
is thyrotoxicosis.
necessary to normalize thyroid
When
a -blocker cannot
be used,the
administration
of aremains
non-dihydropyridine
function
prior
to cardioversion,
as otherwise
risk of relapse
high.
IC
Ifcalcium
a rhythm
control
strategy
is
desirable,
it
is necessary
to normalize
channel antagonist (diltiazem or verapamil)
is recommended
to thyroid
control
IC
IC
function
prior torate
cardioversion,
as otherwise
the risk of relapse remains high.
the ventricular
in patients with
AF and thyrotoxicosis.
Once a euthyroid state is restored, recommendations for antithrombotic
prophylaxis
the
as for
patients
without recommendations
hyperthyroidism.
Once
a same
euthyroid
state
is isrestored,
antithrombotic
IC
IC
Ifare
a rhythm
control
strategy
desirable,
it is necessary tofor
normalize
thyroid
IC
prophylaxis
are
same as foras
patients
without
hyperthyroidism.
function prior
to the
cardioversion,
otherwise
the risk
of relapse remains high.
AF is rare AF
during
pregnancy
and usually
has an
underlying
is rare
during pregnancy
and usually
hasidentifiable
an identifiable
underlying cause,
cause,
such as: such
as:
9.5. PREGNANCY
167
167
ois Mitral
stenosis,
o MitralAF
stenosis,
rare during
pregnancy and usually has an identifiable underlying cause,
168
such
o as:
congenital heart disease,
or
168
169
167
o hyperthyroidism.
or
o Mitral stenosis,
169
o hyperthyroidism.
A o
rapid
ventricular
response168 or
to AF
congenital
heart disease,
can
have
serious
hemodynamic
A rapid ventricular
AF and
can
serious
hemodynamic
consequencesresponse
for both169
the to
mother
the have
foetus. In
a pregnant
woman who
oforhyperthyroidism.
develops
AF, diagnosis
and and
treatment
of the underlying
condition
causingwho
the
consequences
both
the mother
the foetus.
In a pregnant
woman
arrhythmia
the
firsttreatment
priorities.
A diagnosis
rapid are
ventricular
response oftothe
AFunderlying
can have condition
serious hemodynamic
develops AF,
and
causing the
consequences
for both the mother and the foetus. In a pregnant woman who
arrhythmia are
the first priorities.
Digoxin, a beta blocker, or non-dihydropyridine calcium channel antagonist is
IC
Keypoints
a beta blocker, or non-dihydropyridine calcium channel antagonist is
Digoxin,
170-172
recommended
to control
ventricular
rate
in pregnant
patients.
Propranolol
andthe
metoprolol
be the
beta-blockers
of channel
choice, while
atenolol
a beta
blocker,
orwould
non-dihydropyridine
calcium
antagonist
is
Digoxin,
ICIC
is contraindicated. Atenolol given in the rst trimester, but not 170-172
later, has been
recommended to control the ventricular rate in pregnant patients.
with foetal
growth
retardation.
Use ofofbeta-blockers
in atenolol
the first
Propranololassociated
and metoprolol
would
be the
beta-blockers
choice, while
trimester
is toand
be metoprolol
preferably avoided.
Propranolol
would
thetrimester,
beta-blockers
choice,
while
is contraindicated.
Atenolol
given in
the be
rst
butofnot
later,
hasatenolol
been
iswith
contraindicated.
Atenolol
given in the
rst of
trimester,
but not later,
has been
associated All
foetal available
growth
retardation.
Use
beta-blockers
in cross
the
first
currently
drugs
have
potential to
the
associated
with foetal antiarrhythmic
growth retardation.
Use
ofthe
beta-blockers
in the first
trimester is placenta
to be preferably
avoided.
and
breast
milk
and should therefore be avoided if possible.
trimester
is toenter
be preferably
avoided.
171
173
173
and flecainide
havehave
all been
used successfully
for
Quinidine,
61
All currently
antiarrhythmic
drugs drugs
have
the
potential
totocross
All available
currently sotalol,
available
antiarrhythmic
the
potential
cross the
the
pharmacological
cardioversion
during
pregnancy,
however,
relatively small
placenta
and enter
breast
and
should
therefore
be avoided
if possible.
placenta and
enter breast
milk
andmilk
should
therefore
be avoided
if in
possible.
numbers of cases.
IC
frequentlythromboembolism
associated with conditions
that carry a high
risk of thromboembolism,
Protection against
is recommended
throughout
pregnancy for
including congenital or valvular heart disease.
patients with AF except those at low thromboembolic risk. The choice of
anticoagulant
or aspirin
should
be chosen according
to the throughout
stage of pregnancy.
Protection
against
thromboembolism
is recommended
pregnancy for
ICIC
anticoagulant
be chosen warfarin
according to
the stageitof crosses
pregnancy.the
Consideration
should or
beaspirin
givenshould
to avoiding
because
placental barrier and is associated with teratogenic embryopathy in the first
172-179 the
Consideration
should
be
given
to
avoiding
warfarin
because
it
trimester and with foetal haemorrhage in the later stages of pregnancy.crosses
placental barrier and is associated with teratogenic embryopathy in the first
trimester and with foetal haemorrhage in the later stages of pregnancy. 172-179
Heparin is the preferred anticoagulant because it does not cross the placenta.
Heparin is the preferred anticoagulant because it does not cross the placenta.
9.6 HYPERTROPHIC
CARDIOMYOPATHY
developing AF
compared with the general population, and around 20 25%
develop AF with an annual incidence of 2%.
62
B
IB
B
IB
Ia C
IIa C
Ia C
IIa C
Ia C
IIa C
IC
IC
IIIC
IIIC
IIIC
IIIC
IC
IC
patients with
bronchospastic lung disease who develop AF.
correction of hypoxemia and acidosis are the primary therapeutic measures.
Beta-blockers,
sotalol,and
propafenone,
andagonist
adenosine
contraindicated
Theophylline
beta-adrenergic
agents are
are not
recommended in
in
IIIC
patients
with bronchospastic lung disease who develop AF.
bronchospasm.
patients with
Beta-blockers,
propafenone,
and adenosine
are contraindicated
in
Diltiazem
or
verapamil issotalol,
recommended
to control
the ventricular
rate in patients
IIIC
patients with bronchospasm.
with obstructive
pulmonary disease who develop AF with or without digoxin.
Diltiazem or verapamil is recommended to control the ventricular rate in patients
alternative
for ineffective
ventricular rate
control.AF unless respiratory decompensation
Cardioversion
may be
against
has been corrected.
Cardioversion may be ineffective against AF unless respiratory decompensation
has been corrected.
In patientsInwith
AF and
pulmonary
disease,
the general
recommendations
patients
with AF
and pulmonary
disease,
the general
recommendations for
for
antithrombotic
therapy apply.
antithrombotic
therapy apply.
HEART FAILURE
9.8 HEART9.8
FAILURE
AF is a strong and independent risk factor for the development of heart failure,
AF is a strong
and conditions
independent
risk factor
for17,183
theThe
development
failure,
onset of AFof
in heart
a patient
with
and both
frequently
co-exist.
17,183
The onset of
AF in a topatient
with
and both conditions
co-exist.
heart failure frequently
often leads to
symptomatic deterioration,
predisposes
episodes
of
heart failure
often leads
symptomatic
deterioration,
predisposes toepisodes,
episodesand
of
worsening
hearttofailure,
increases
the risk of thrombo-embolic
long-term
outcome. the risk of thrombo-embolic episodes, and
worsening worsens
heart failure,
increases
worsens long-term outcome.
In the initial approach to heart failure patients with AF, the following issues need
to be considered:17
In the initial approach to heart failure patients with AF, the following issues need
17
to be considered:
x Potential precipitating factors and secondary causes should be identied
x
x
Potential
factors
and
secondary
should be identied
x precipitating
Background heart
failure
treatment
shouldcauses
be optimized.
and if possible corrected.
When
ventricular
rate
control
is
required
in
patients
with
heart
Background heart failure treatment should be optimized. failure and AF, -
When ventricular rate control is required in patients with heart failure and AF, blockers are preferred over digitalis glycosides due to their rate-controlling effect
during exertion rather than only at rest. A combination of digoxin and a -blocker
may be more effective than a single drug for heart-rate control at rest. Therapy
with -blockers alone or in combination with digoxin was associated with lower
mortality rates compared with treatment with digoxin alone.184
-Blockers have favourable effects on mortality and morbidity in patients with
systolic heart failure. A recent meta-analysis also showed a 27% reduction in the
incidence of new-onset AF in patients with systolic heart failure treated with blockers.185
Although diltiazem effectively controls excessive heart rate during exercise, it
adversely suppresses myocardial contraction and increases the risk of heart
failure. For patients with heart failure and preserved ejection fraction, these drugs
used in combination with digoxin appear to be more effective in controlling heart
rate over 24 h and during exercise than digoxin or non-dihydropyridine calcium
channel antagonist monotherapy.
The rhythm control strategy has not been shown to be superior to rate control in
heart failure patients with AF.27 Catheter-based LA ablation procedures in heart
failure patients may lead to improvement in LV function, exercise tolerance, and
quality of life in selected patients (see Section 8.3.1).29,30
64
The prevention of thrombo-embolism is covered in Section 6, but the presence of
heart failure due to systolic dysfunction is itself a risk factor for stroke and
Although
effectively than
controls
excessive
heart rate during exercise,
it
rate over 24
h anddiltiazem
during exercise
digoxin
or non-dihydropyridine
calcium
adversely monotherapy.
suppresses myocardial contraction and increases the risk of heart
channel antagonist
failure. For patients with heart failure and preserved ejection fraction, these drugs
used in combination with digoxin appear to be more effective in controlling heart
The rhythmrate
control
strategy
has not
been than
shown
to be
to rate control
in
over 24
h and during
exercise
digoxin
or superior
non-dihydropyridine
calcium
27
Catheter-based LA ablation procedures in heart
heart failure
patients
with AF.
channel
antagonist
monotherapy.
failure patients may lead to improvement in LV function, exercise tolerance, and
Theinrhythm
control
strategy
hasSection
not been8.3.1).
shown29,30
to be superior to rate control in
quality of life
selected
patients
(see
27
heart failure patients with AF.
IC
Keypoints
DCCV is recommended when a rapid ventricular rate does not respond to
DCCV ismeasures
recommended
a rapid
rate ongoing
does not myocardial
respond to
pharmacological
in when
patients
withventricular
AF and
I CIC
measures inorpatients
withofAF
and ongoing
myocardial
ischaemia,pharmacological
symptomatic hypotension,
symptoms
pulmonary
congestion.
IC
In patientsInwith
AF with
and AF
severe
(NYHA(NYHA
classclass
III or
or orrecent
patients
and severe
III IV)
or IV)
recent (<4
(<4 weeks)
weeks)
unstable
heart
failure,
use the
of antiarrhythmic
therapy
to maintain
I CIC
unstable
heartthe
failure,
use of antiarrhythmic
therapy
to maintainsinus
sinus rhythm
rhythm
should be restricted
to amiodarone.
should be restricted
to amiodarone.
IIa B
IIa C
IIb B
IIb B
of amiodarone
a reasonable
optionforforpharmacological
pharmacological
Administration
of amiodarone
is a isreasonable
option
Administration
21,39,45,186
IIa
B
IIaB
cardioversion of AF, or to facilitate electrical cardioversion of AF.
cardioversion
of AF, or to facilitate electrical cardioversion of AF.21,39,45,186
In patients with AF and stable heart failure (NYHA class I, II) dronedarone should
C
IIaC
InIIa
patients
with
AF and to
stable
heart
failure (NYHA
class I, II) dronedarone should
be
considered
reduce
cardiovascular
hospitalizations.
For patients
with
heart failure
and
symptomatic
persistent AF despite adequate
be considered to reduce cardiovascular hospitalizations.
rate control,
electrical
cardioversion
and rhythm
be
For patients
with heart
failure and symptomatic
persistent control
AF despitemay
adequate
27,29,30,32,187
IIb
B
IIbB
rate
control, electrical cardioversion and rhythm control may be
considered.
27,29,30,32,187
considered.
Rate control
is difficult tocalcium
achieve
in athletes.
are not
well heart
tolerated
dihydropyridine
antagonists
will not-blockers
be potent enough
to slow
rate
duringbe
exertional
AF. in some competitive sports, and digoxin or nonand may even
prohibited
dihydropyridine calcium antagonists will not be potent enough to slow heart rate
When the heart rate during AF is acceptable at maximal physical performance for
during exertional
AF.
a given athlete without signs of haemodynamic impairment (dizziness, syncope,
sudden fatigue), competitive sports activity can be resumed.
When the heart rate during AF is acceptable at maximal physical performance for
a given athlete
without
signs when
of haemodynamic
(dizziness,
syncope,
Caution
is necessary
using flecainide impairment
and propafenone
as monotherapy
in
maycan
leadbe
to resumed.
atrial utter, with 1 to 1 conduction
athletes
with AF.192 These
sudden fatigue),
competitive
sportsdrugs
activity
to the ventricles during high sympathetic tone. Therefore, ablation of the utter
65
193 for
In some athletes
with paroxysmal
AF,such
ecainide
or ablation
propafenone
be used
Non- pharmacological
options
as catheter
can be can
considered.
acute conversion (the pill-in-the-pocket approach; see Section 5.1.2.1).42 These
cessation
should
consideredinforcompetitive
as long as the
persists,
andwith
until
Isthmus ablation
should
bebe
considered
or arrhythmia
leisure-time
athletes
12 half-lives of the antiarrhythmic drug used have elapsed.
documented atrial utter, especially when therapy with ecainide or propafenone
is intended.Isthmus ablation should be considered in competitive or leisure-time athletes with
IIa
C
IIaC
IIa C
documented
atrial utter, especially
therapychannel
with ecainide
When a pill-in-the-pocket
approachwhen
with sodium
blockersorispropafenone
used, sport
IIa
C
IIaC
IIa C
ablation
should
be cause.
considered to prevent recurrent AF in
orWhere
leisureappropriate,
time sportsAF
until
correction
of the
iscessation
intended.
Where appropriate,
AF
ablation
should be
prevent recurrent
AFuntil
in
should
be considered
for considered
as long as thetoarrhythmia
persists, and
12 half-lives of the antiarrhythmic drug used have elapsed.
athletes.
When a specic
cause(such
for as
AFdizziness)
is identied
in an athlete (such as
haemodynamic
impairment
are present.
hyperthyroidism), it is not recommended to continue participation in competitive
or leisure time sports until correction of the cause.
9.10 VALVULAR
HEART DISEASE
9.10 VALVULAR
HEART DISEASE
It is not recommended to allow physical sports activity when symptoms due to
III C
haemodynamic
impairment
(such
as dizziness)
are
present.
AF frequently
accompanies
valvular
heart
disease.
LA distension
early
AF frequently
accompanies
valvular
heart
disease.
LA
distension
is isananearly
manifestation
of progressive
disease,
presence of
of
manifestation
of progressive
mitral mitral
valve valve
disease,
andand
thethepresence
paroxysmal
or
permanent
AF
is
an
accepted
indication
for
early
percutaneous
or
paroxysmal or
permanent
AF
is anDISEASE
accepted indication for early percutaneous or
66
9.10
VALVULAR
HEART
AF is also frequently seen in later stages of aortic
surgical mitral intervention.
surgical mitral
intervention.66 AF is also
frequently seen in later stages of aortic
valve disease when LV dilatation and elevated end-diastolic pressure exert
valve disease
when
LV
dilatation
and
elevated
end-diastolic
pressure
AF
frequently
accompanies
valvular
heart disease.
LA distension
is anexert
early
secondary effects on LA function.
manifestation
of progressive mitral valve disease, and the presence of
secondary effects
on LA function.
paroxysmal orofpermanent
AF conventional
is an acceptedrecommendations
indication for earlyinpercutaneous
Management
AF follows
the setting or
of
66
AF isaalso
in later
stages of
aortic
surgical heart
mitral disease,
intervention.
valvular
although
ratefrequently
control seen
strategy
usually
adopted
Management
of AF
follows
conventional
recommendations
inis the
setting
of
valve
disease
when
LV
dilatation
and
elevated
end-diastolic
pressure
exert
because
of the low
likelihoodaofrate
maintaining
rhythm in
long term.
valvular heart
disease,
although
controlsinus
strategy
is the
usually
adopted
secondary
effects
on LA function.
III C
because of the low likelihood of maintaining sinus rhythm in the long term.
valvular surround
heart disease,
although a rate control strategy is usually adopted
Principal concerns
(See Section
6.1). the high risk of thrombo-embolism in subjects with
of the
lowa likelihood
of maintaining
sinus rhythm inisthe
long term.
valvular heartbecause
disease,
and
low threshold
for anticoagulation
recommended
(See SectionPrincipal
6.1). concerns surround the high risk of thrombo-embolism in subjects with
IC
OAC therapy (INR 2.03.0) is indicated in patients with mitral stenosis and AF
valvular heartpersistent,
disease, and
a low threshold for anticoagulation is recommended
(paroxysmal,
or permanent).
(See Section 6.1).
Keypoints
OAC
therapy (INR 2.03.0) is indicated in patients with mitral stenosis and AF
OAC therapy (INR 2.03.0) is recommended in patients with AF and clinically
IC
(paroxysmal,
persistent,
permanent).
signicant
mitralorregurgitation.
I CIC
OAC therapy (INR 2.03.0) is indicated in patients with mitral stenosis and AF
(paroxysmal, persistent, or permanent).
OAC therapy
(INR 2.03.0)
recommended
in patients
with AFforand
clinically
Percutaneous
mitral is
balloon
valvotomy should
be considered
asymptomatic
IIa C
patients
with moderate
or severe
mitral stenosisinand
suitable
valve
who
signicant
mitral
OAC regurgitation.
therapy
(INR 2.03.0)
is recommended
patients
with
AF anatomy
and clinically
I CIC
have
new-onset
in the absence of LA thrombus.
signicant
mitralAF
regurgitation.
IC
OAC therapy (INR 2.03.0) is indicated in patients with mitral stenosis and AF
(paroxysmal, persistent, or permanent).
IC
IIaC
IIa
C
IIa
C
IIaC
10. REFERRALS
10.1 Acute hospitalisation/referral
This is required for patients with:
x AF/AFL with haemodynamic compromise, acute dyspnoea, acute heart
failure, chest pain, ischaemia, near syncope, hypotension
x AF/AFL with rapid uncontrolled heart rate, e.g., over 140 bpm at rest
x AF/AFL with acute systemic illness requiring acute management
x rst/new onset of AF/AFL symptoms, no contraindications to cardioversion,
with the possibility of cardioversion within 48 hours of onset.
10.2 Outpatient specialist physician/cardiologist
Outpatient specialist referral is recommended for those who:
x Need further investigation/echocardiography
x Have suspected structural heart disease (e.g., hypertensive, valvular,
ischaemic)
x Are to be considered for cardioversion
x Are highly symptomatic, requiring maintenance of sinus rhythm
antiarrhythmic therapy
x Are having difficulty with pharmacological rate control
x Require a second opinion of the risk/benet ratio of anticoagulation
x Are having syncopal attacks.
10.3 Cardiac electrophysiologist (heart-rhythm specialist)
Tertiary referral is recommended for patients who have:
x AF with WPW syndrome (pre-excited AF)
x Highly-symptomatic AF unresponsive to rst-line antiarrhythmic treatment
x Uncontrolled ventricular rate with maximally tolerated atrioventricularblocking therapy
x Recurrent AFL (including mixed AFL and AF where AFL is the dominant
arrhythmia)
x Tachycardia-bradycardia syndrome (sinus node dysfunction)
x Suspicion or documentation of a regular tachycardia triggering AF (e.g.,
SVT).
10.4 No referral
Referral is not needed for patients who have rate-controlled AF with mild or
occasional symptoms, for whom echocardiography is not required (e.g.,
previously obtained), and for whom the decision regarding stroke prevention
management is clear cut.
67
Exception
None.
Definition of terms
Percentage of patient
records with a new
diagnosis of AF made
following an ECG made
on the basis of detection
of an irregular pulse.
Haemodynamically
unstable patients or
those in whom
assessment is impossible
or inappropriate.
Percentage of patient
records with a
documentation of risk
assessment and
thromboprophylaxis
consistent with the stroke
risk stratification
algorithm.
Haemodynamically
unstable patients or
those in whom
assessment is impossible
or inappropriate.
Percentage of patient
records with a
documentation of risk
assessment for bleeding
consistent with the
bleeding risk stratification
algorithm.
Percentage of patient
records with a
documentation of
involvement of the patient
in the decision- making
process.
Postoperative or
haemodynamically
unstable patients, or
those otherwise not able
to engage in a decisionmaking process.
None.
Percentage of patient
records with a
prescription of digoxin for
68
initial rate-control
monotherapy where the
reason for digoxin
prescription is:
Sedentary patient
Presence of contraindications to betablockers
or rate-limiting calcium
Antagonists
Other reasons.
None.
Percentage of patient
records with a
prescription of
amiodarone for long-term
rhythm-control therapy
where the reason for
amiodarone prescription
is:
Presence of contraindications to betablockers, dronedarone,
flecainide or propafenone
Other reasons.
69
APPENDIX A
Search Terms
Scope of search
A literature search was conducted for guidelines, systematic reviews and
randomized controlled trials on the primary care management of Atrial
fibrillation, with additional searches in the following areas:
Outpatient therapy
Rhythm versus rate control
Anti-arrhythmics for cardioversion
Drugs for rate control
Anticoagulation versus antiplatelet drugs to prevent thromboembolism
Stroke risk versus bleeding risk
Invasive or emerging therapies
Referral criteria
Search dates
January 2010 December 2011
Key search terms
Various combinations of searches were carried out. The terms listed below are
the core search terms that were used for Medline and these were adapted for
other databases.
APPENDIX B
Clinical questions
A. Introduction
1. What is the best way to classify atrial fibrillation?
2. What is the epidemiological characteristic of atrial fibrillation?
B. Initial management
1. What are the frequencies of the presenting symptoms?
2. In patients with suspected AF based on an irregular pulse, how accurate
is an ECG in diagnosing AF?
3. Should echocardiography be performed to identify underlying structural
heart disease?
4. In patients with suspected intermittent AF, how effective is ambulatory
ECG compared to an event ECG in diagnosing AF?
5. Which patients with AF would benefit from referral to specialist?
C. Management principles
1. In which patients with persistent AF does rate control result in improved
mortality/morbidity/quality of life over rhythm control?
2. In which patients with persistent AF does rhythm control result in
improved mortality/morbidity/quality of life over rate control?
D. Acute-onset AF
1. In haemodynamically unstable patients presenting with acute AF, what
is the best treatment strategy?
2. In which patients should pill-in-the-pocket therapy be recommended?
3. Does electrical cardioversion versus pharmacological cardioversion
affect rates of thromboembolism, quality of life, success rates?
4. In patients with persistent AF, is amiodarone better than a) flecainide or
b) propafenone for use in cardioversion?
5. In patients with persistent AF is amiodarone better than sotalol for use
in cardioversion?
6. What is the safety and efficacy of the adjunctive administration of
antiarrhythmic drugs for use in electrical cardioversion in comparison to
electrical cardioversion without adjunctive antiarrhythmic drugs?
7. Is a conventional anticoagulation strategy for elective cardioversion as
effective as a transoesophageal echocardiogram plus anticoagulation?
E. Prevention of thromboembolism
1. In patients with AF, what are the risk factors associated with stroke/TIA
and thromboembolism?
2. What is the efficacy of anticoagulation therapy versus placebo for
stroke prevention in: a) paroxysmal AF b) permanent AF c) peri/post
cardioversion to sinus rhythm d) acute/post-op AF e) peri/post stroke f)
72
asymptomatic AF?
3. What is the efficacy of anticoagulation therapy versus antiplatelet
therapy for stroke prevention in: a) paroxysmal AF b) permanent AF c)
peri/post cardioversion to sinus rhythm d) acute/post-op AF e) peri/post
stroke f) asymptomatic AF?
4. What is the efficacy of antiplatelet therapy versus placebo for stroke
prevention in: a) paroxysmal AF b) permanent AF c) peri/post
cardioversion to sinus rhythm d) acute/post-op AF e) peri/post stroke f)
asymptomatic AF?
5. What is the efficacy of vitamin K antagonist versus novel anticoagulant
for stroke prevention in: a) paroxysmal AF b) permanent AF c) peri/post
cardioversion to sinus rhythm d) acute/post-op AF e) peri/post stroke f)
asymptomatic AF?
6. What is the role of point-of-care testing and self-monitoring of
anticoagulation.
7. How best to institute anticoagulant and antiplatelet therapy in patients
with AF undergoing percutaneous coronary intervention and non-ST
elevation myocardial infarction
8. In patients with AF what are the risks of long-term oral anticoagulation
therapy?
9. In patients with AF and vitamin K antagonist, what are the risk factors
associated with bleeding?
F. Long-term rate control
1. In patients with permanent AF, what is the efficacy of rate-limiting
calcium antagonists compared with digoxin in rate control?
2. In patients with permanent AF, what is the efficacy of beta-blockers
compared with digoxin in rate control?
3. In patients with permanent AF, what is the efficacy of beta-blockers
compared with rate-limiting calcium antagonists in rate control?
4. In patients with permanent AF, what is the efficacy of rate-limiting
calcium antagonists in combination with digoxin compared with ratelimiting calcium antagonists monotherapy in rate control?
5. In patients with permanent AF, what is the efficacy of beta-blockers in
combination with digoxin compared with beta-blocker monotherapy in
rate control?
6. In patients with permanent AF, what is the efficacy of AV node ablation
with permanent pacemaker therapy in rate control?
G. Long-term rhythm control
1. In patients with paroxysmal AF, is flecainide/propafenone better than
beta-blockers in reducing the frequency of paroxysms?
2. In patients with paroxysmal AF, is amiodarone or sotalol better than
beta-blockers in reducing the frequency of paroxysms?
3. In patients with paroxysmal AF, is flecainide/propefanone better than
amiodarone or sotalol in reducing the frequency of paroxysms?
73
4. In patients with AF, is flecainide or propafenone better than betablockers in maintaining sinus rhythm post cardioversion?
5. In patients with AF, is amiodarone or sotalol better than beta-blockers
in maintaining sinus rhythm post cardioversion?
6. In patients with AF, is flecainide/propafenone better than amiodarone or
sotalol in maintaining sinus rhythm post cardioversion?
7. Which antiarrhythmic agents should be chosen to maintain sinus rhythm
for patients with normal hearts?
8. Which antiarrhythmic agents should be chosen to maintain sinus rhythm
for patients with structural heart disease?
9. What is the efficacy of left atrial catheter ablation and surgical ablation
therapy for rhythm control in patients with a) paroxysmal AF b) persistent
AF?
10. What is the efficacy of cardiac pacing therapy for rhythm control in
patients with paroxysmal AF?
H. Referrals
1. Which patients with AF benefit from referral to specialist services for
assessment and management?
2. Which patients with AF benefit from referral to specialist services for
non-pharmacological treatment or electrophysiological studies?
APPENDIX C
C. WARFARIN IN PRACTICE
Barriers that may prevent people accessing medication and INR testing include:
Financial barriers (including the ability to take time off work)
Travel difficulties
Lack of access to a telephone
Fear or dislike of regular blood tests
Difficulties with general practitioner monitoring.
Possible solutions include the following:
Financial assistance from relevant agencies
Provision of transport (e.g., shuttle service, taxi chits)
Domiciliary testing, either at home or the work place
Testing people in groups at a public health centre using a point-of-care monitor
C.1 INITIATION OF WARFARIN THERAPY
Loading doses are not recommended because they may increase the risk of
bleeding
Initiation of warfarin should be 5 mg daily in most patients (usually achieves INR
2 in 4-5 days)
A starting dose < 5 mg should be considered for patients >65 yrs, liver disease,
malnourished, severe heart failure, 74
or concomitant drugs affecting warfarin
metabolism.
outpatient transition more convenient. It is the most commonly used size tablet
by the majority of anticoagulation clinics today.
The higher dose warfarin initiation has also been tested successfully by using
normogram. It may be considered in patient who may need shorter period of time
to reach therapeutic INR. It should be done as inpatient. INR have to be done
frequently enough to prevent over anticoagulation and bleeding complication
Use lower dose (2.5 mg).
x >80 yr.
x Concurrent illness.
x On interaction drug.
x S/P major surgery, i.e. heart valve surgery.
x Chronic malnourished.
x Impaired liver function, liver congestion.
Use higher dose (7.5-10.0 mg).
x Young healthy subject.
x In the first two days.
Day 2
A. If INR <1.5, continue the same dose.
B. If INR >1.5, give lower dose (2.5 mg or none)
Day 3
For #A. of Day 2
x If INR <1.5, suggests a higher than average maintenance dose of 5
mg/day or 35 mg/week will be needed. Give higher dose than 5 mg. i.e.7.5
mg for now.
x If INR 1.5-2.0, suggests an average maintenance dose close to 5 mg/day
or close to 35 mg/week will be needed, and continue 5 mg for now.
x If INR >2.0, suggests a lower than average maintenance dose of 5 mg/day
or 35 mg/week will be needed. Give less than 5 mg, i.e.2.5 mg or none for
now.
For #B. of Day 2
x If INR 1.5-2.0, suggests daily dose will be close to or less than 5 mg/day
or close to 35 mg/week or less. May give 5 mg or less for now.
x If INR >2.0, suggests daily dose will be lower than 5 mg/day or less than
35 mg/week. May give 2.5 mg or none for now.
Day 4
If there is no need for heparin therapy, the patient may have been discharged by
now, and warfarin initiation is continued as an outpatient.
x INR 2 times a week until INR is in target range twice in a row, then INR 1
time weekly until INR is in target range twice in a row, then INR 1 time in 2
week until INR is in target range twice in a row, then enter the patient in to
maintenance schedule (usually INR every 4 weeks).
x Patients during an acute illness, or post operative of major surgeries may
be more sensitive to warfarin than when they become more stable.
Out patient (See also "Day 4" above)
x
x
x
77
C.1.7 Ethnic Difference for Chinese-Asian or Pacific-Asian (exclude caucasian in
x
x
x
DOSE
INPATIENT
OUTPATIENT
Normal
5.0 mg
(2.5 or 7.5-10.0 mg in patients listed in the
text)
5.0 mg
(2.5 or 7.5-10.0 mg in patients listed in the text)
< 1.5
> 1.5
5.0 mg
0.0 - 2.5 mg
5.0 mg
0.0 - 2.5 mg
< 1.5
1.5 - 1.9
2.0 - 3.0
> 3.0
5.0 - 10 mg
2.5 - 5.0 mg
0.0 - 2.5 mg
0.0 mg
< 1.5
1.5 - 1.9
2.0 - 3.0
> 3.0
10.0 mg
5.0 - 7.5 mg
0.0 - 5.0 mg
0.0 mg
10.0 mg
5.0 - 7.5 mg
0.0 - 5.0 mg
0.0 mg
< 1.5
1.5 - 1.9
2.0 - 3.0
> 3.0
10.0 - mg
7.5 - 10.0 mg
0.0 - 5.0 mg
0.0 mg
10.0 - mg
7.5 - 10.0 mg
0.0 - 5.0 mg
0.0 mg
INR measurement should be done, if INR on day 4 is < 1.5
or > 3.0
< 1.5
1.5 - 1.9
2.0 - 3.0
> 3.0
7.5 - 12.5 mg
5.0 - 10.0 mg
0.0 - 7.5 mg
0.0 mg
7.5 - 12.5 mg
5.0 - 10.0 mg
0.0 - 7.5 mg
0.0 mg
78
DOSE
DAY
INR
Normal
1
< 1.3
> 1.3
INPATIENT
(Usually with daily INR)
OUTPATIENT
3.0 mg
(1.5 or 3.0-6.0 mg in patients listed in the text)
3.0 mg
(1.5 or 3.0-6.0 mg in patients listed in the text)
3.0 mg
0.0 - 1.5 mg
3.0 mg
0.0 - 1.5 mg
[If INR is not measured
3.0 mg (1.5-4.5)]
< 1.3
1.3 - 1.6
1.6 - 2.6
> 2.6
3.0 - 6 mg
1.5 - 3.0 mg
0.0 - 1.5 mg
0.0 mg
3.0 - 6 mg
1.5 - 3.0 mg
0.0 - 1.5 mg
0.0 mg
INR should be measured today. If INR is not measured,
may use the same dose as day 2, and should not > 3.0 mg
< 1.3
1.3 - 1.6
1.6 - 2.6
> 2.6
4.5 - 6.0 mg
3.0 - 4.5 mg
1.5 - 3.0 mg
0.0 mg
< 1.3
1.3 - 1.6
1.6 - 2.6
> 2.6
6.0 - 7.5 mg
3.0 - 4.5 mg
1.5 - 3.0 mg
0.0 mg
4.5 - 6.0 mg
3.0 - 4.5 mg
0.0 - 3.0 mg
0.0 mg
INR measurement should be done, if INR on day 3 is < 1.3
or > 2.6
6.0 - 7.5 mg
3.0 - 4.5 mg
1.5 - 3.0 mg
0.0 mg
INR measurement should be done, if INR on day 4 is < 1.3
or > 2.6
< 1.3
1.3 - 1.6
1.6 - 2.6
> 2.6
6.0 - 7.5 mg
4.5 - 6.0 mg
1.5 - 3.0 mg
0.0 mg
6.0 - 7.5 mg
4.5 - 6.0 mg
1.5 - 3.0 mg
0.0 mg
INR measurement should be done, if INR on day 5 is < 1.3
or > 2.6
Note: Frequent INR measurement during warfarin initiation helps prevent bleeding from over anticoagulation and helps reaching target INR sooner.
C.1.8
Dose
2.0-3.0)
C.1.8
DoseAdjustments
Adjustmentsfor
forWarfarin
WarfarinMaintenance
Maintenance Therapy
Therapy (Target INR 2.0-3.0)
INR
INR
1.5
1.5
1.5-1.9
1.5-1.9
2.0-3.0
2.0-3.0
3.1-3.9
3.1-3.9
4.0-5.0
4.0-5.0
!5.0
!5.0
Dose Adjustments
Adjustments
Dose
Increaseweekly
weekly dose
dose by
by 20%
Increase
Increaseweekly
weekly dose
dose by 10%
Increase
No change
change
No
Nochange;
change;ififpersistent
persistentdecrease
decrease weekly
weekly dose
dose by
No
by 10-20%
10-20%
Omit11dose;
dose;decrease
decrease weekly
weekly dose
dose by
by 10-20%
Omit
10-20%
Seerecommendations
recommendations for
for managing
managing elevated
elevated INR
See
INR
Whenresume
resumedecrease
decrease weekly
weekly dose
dose 20-50%
20-50%
When
79
C.1.8.1
Recommendationsfor
forManaging
ManagingElevated
ElevatedINRs
INRs or
or Bleeding
Bleeding in Patients
C.1.8.1
Recommendations
C.1.8.1
Recommendations
for Managing Elevated INRs or Bleeding in Patients
Receiving
Warfarin:
Receiving
Warfarin:
Receiving Warfarin:
Condition
Recommendation
Condition
Recommendation
Condition
Recommendation
INR
above
Lowerthe
thedose
doseororomit
omit
doseand
and resume
resume with
with lower
lower dose
INR
above
Lower
aadose
dose
INR
aboverange
Lower
thetherapeutic;
dose
or omitififaonly
dose
and resume
with
lower dose
therapeutic
range when
whenINR
INR
therapeutic;
only
minimally
above
therapeutic
therapeutic
minimally
above
therapeutic
when
INR
therapeutic;
if only
above therapeutic
range,no
nodose
dose
reduction
mayminimally
be required.
required.
but
5;
buttherapeutic
5;
nono range range,
reduction
may
be
but
5; no
significant
bleeding range, no dose reduction may be required.
significant
bleeding
significant
bleeding Omitnext
nextone
oneorortwo
twodoses,
doses,monitor
monitor INR
INR more
more frequently,
frequently,
INR
t but
5 but
INR
t5
9;9;nono Omit
Omit
next one
orlower
two doses,
monitor
INR
more frequently,
INR
t 5 but
9; no and
andresume
resume
with
lower
dosewhen
when
INR
therapeutic.
If
significant
bleeding
with
dose
INR
therapeutic.
If risk
risk of
of
significant
bleeding
and
resume
with
dose and
when
INRvitamin
therapeutic.
If risk
significant bleeding bleeding,
bleeding,
omit
thelower
nextdose
and give
give
vitamin
K 1-2.5
1-2.5
mg
omit
the
next
K
mg of
bleeding,
omit the next dose and give vitamin K 1-2.5 mg
PO.
PO.
PO.
Holdwarfarin
warfarinand
andgive
giveVitamin
VitaminKK 2.5-5
2.5-5 mg
mg orally;
orally; expect
INR
t 9;
Hold
expect
INR
t 9;
nono
warfarin
and
give Vitamin
K 2.5-5Monitor
mg orally;
INR
t 9; nobleeding Hold
substantial
INR
reduction
in 24-48hr.
INRexpect
more
significant
INR reduction in 24-48hr. Monitor INR more
significant bleeding substantial
INRrepeat
reduction
in 24-48hr.
Monitor Resume
INR more
significant bleeding substantial
frequently and
vitamin
K if necessary.
frequently
and
repeat
vitamin
K
if
necessary.
Resume
frequently
repeat vitamin
K if necessary.
Resume
warfarin atand
an adjusted
dose when
INR therapeutic.
warfarin
warfarinatatan
anadjusted
adjusteddose
dosewhen
when INR
INR therapeutic.
therapeutic.
Serious bleeding at Hold warfarin and give vitamin K 10 mg slow IV infusion,
Serious
bleeding
warfarin
give
vitamin
KK 10
slow
infusion,
Serious
bleeding
Hold
warfarinand
and
give
vitamin
10 mg
mg
slow IV
IVconcentrate
infusion,
any elevation
ofatat Hold
supplemented
with
FFP,
prothrombin
complex
any
elevation
supplemented
with
prothrombin
complex
concentrate
any
elevationofof
supplemented
withFFP,
FFP,
prothrombin
complex
concentrate
INR
or rVIIa, depending
on urgency
of situation.
Vitamin
K can
INR
oror
rVIIa,
depending
on
urgency
of
situation.
Vitamin
K can
can
INR
rVIIa,
depending
on
urgency
of
situation.
Vitamin
K
be repeated q12hr
be
repeated
q12hr
be
repeated
q12hr
Life threatening
Hold warfarin and give FFP, prothrombin complex
Life
threatening
Hold
warfarin
give
FFP,
complex
Life
threatening
Hold
warfarinand
and
give
FFP,prothrombin
prothrombin
complex
bleeding
concentrate,
or
rVIIa
supplemented
with vitamin
K 10 mg
bleeding
concentrate,
ororrVIIa
supplemented
with
vitamin
10
mg
bleeding
concentrate,
rVIIa
supplemented
withdepending
vitamin K
K 10
slow IV infusion.
Repeat,
if necessary,
on mg
INR.
slow
on INR.
INR.
slowIVIVinfusion.
infusion. Repeat,
Repeat,ififnecessary,
necessary, depending
depending on
Recommendations
Recommendations
Stop warfarin 5 daysRecommendations
before surgery allowing INR to return
Stop
warfarin
55days
before
surgery
return
Stop
warfarin
days
before
surgery
allowing
to return
to near
normal.
Bridge
therapy
with allowing
low
doseINR
LMWH
or no
toto
near
no
nearnormal.
normal. Bridge
Bridgetherapy
therapy with
with low
low dose
dose LMWH or no
bridging.
bridging.
bridging.
Stop warfarin 5 days before surgery allowing INR to fall,
Stop
warfarin
dayswith
before
surgery allowing
allowing
to fall,
Stop
55days
before
surgery
INR 2-3
startwarfarin
bridge
therapy
therapeutic
dose LMWH
days
start
bridge
therapy
withtherapeutic
therapeutic
dose LMWH 2-3
priorbridge
to surgery
(or when
INR is sub-therapeutic).
start
therapy
with
dose
days
2-3 days
prior
surgery
(orwhen
when
INRisis24
sub-therapeutic).
Administer
last(or
dose
of LMWH
hrs before surgery.
prior
totosurgery
INR
sub-therapeutic).
Administer
last
dose
of
LMWH
24
hrs
before
surgery.
Stop warfarin
daysofbefore
surgery
INR to fall,
Administer
last 5dose
LMWH
24 hrsallowing
before surgery.
Stop
warfarin
dayswith
before
surgery allowing
allowing
INR 2-3
to
startwarfarin
bridge
therapy
therapeutic
dose LMWH
days
Stop
55days
before
surgery
INR
to fall,
fall,
start
bridge
therapy
with
therapeutic
dose
LMWH
priorbridge
to surgery
(or when
INR is sub-therapeutic).
start
therapy
with therapeutic
dose LMWH 2-3
2-3 days
days
prior
to
surgery
(or
when
INR
is
sub-therapeutic).
Administer
last(or
dose
of LMWH
before surgery.
prior
to surgery
when
INR is 24hrs
sub-therapeutic).
Administer
last
dose
of
LMWH
24hrs
before
surgery.
Lower warfarin
operate
at an
INR of
1.3-1.5; the
Administer
last dose ofand
LMWH
24hrs
before
surgery.
Lower
warfarin
doseand
and
operate
at an
ansurgery;
INR of
of 1.3-1.5;
1.3-1.5;
dose warfarin
may
be lowered
4-5operate
days before
warfarinthe
can
Lower
dose
at
INR
the
dose
may
be
lowered
4-5
days
before
surgery;
warfarin
can
be
restarted
post-op,
supplement
with
LMWH
if
necessary.
dose may be lowered 4-5 days before surgery; warfarin
can
restartedpost-op,
post-op,supplement
supplement with
with LMWH
LMWH ifif necessary.
necessary.
beberestarted
For immediate reversal give FFP, prothrombin complex
For
immediate
reversal
give
FFP, prothrombin
prothrombin
complex
concentrate
inreversal
additiongive
to vitamin
K 2.5-5 mg po
or by slow
For
immediate
FFP,
complex
concentrate
addition to vitamin K 2.5-5 mg po or by slow
IV infusion. ininaddition
concentrate
to vitamin K 2.5-5 mg po or by slow
IV infusion.
IV infusion.
If surgery is urgent but can be delayed for 18-24 hrs give
If surgery is urgent but can be delayed for 18-24 hrs give
If surgery is urgent but can be delayed for 18-24 hrs give
80
other invasive
procedure (within
18-24 hours)
Low risk: VTE: Single VTE occurred >12 months ago and no other risk factors,
AF: (CHADS2 score 0-2) without a history of stroke or other risk factors, Mech
heart valve: bileaflet aortic valve without AF and no other risk factors for stroke.
Moderate risk: VTE: VTE within 3-12 months, non-severe thrombophilic
conditions, recurrent VTE, active cancer, AF: (CHADS2 score 3 or 4), Mech heart
valve: bileaflet aortic valve and one of the following: AF, prior stroke or TIA, HTN,
DM, CHF, age >75 yr.
High risk: VTE: recent (within 3mo) VTE, severe thrombophilia, AF:(CHADS2
score 5 or 6), recent (within 3 months) stroke or TIA, rheumatic valvular heart
disease,
Mech heart valve: any mitral valve prosthesis, older aortic valve prosthesis
(caged-ball or tilting disc), recent (within 6 months) stroke or TIA
x
x
Resume warfarin therapy 12-24 hrs after surgery and when there is
adequate hemostasis.
Resume bridge therapy:
o Minor surgery or other invasive procedure and receiving therapeutic
dose LMWH: Resume 24 hrs after the procedure when there is
adequate hemostasis
o Major surgery or high bleeding risk surgery/procedure where postop therapeutic dose LMWH is planned: delay initiation of
therapeutic dose LMWH for 48-72 hours after surgery when
hemostasis is secured or administering low dose LMWH after
surgery when hemostasis is secured or completely avoiding LMWH
after surgery.
81
APPENDIX D
Vaughn Williams Classification of Antiarrhythmic Drugs
Type IA
Disopyramide
Procainamide
Quinidine
Type IB
Lignocaine
Mexilitine
Type IC
Flecainide
Propafenone
Type II
Beta blockers (e.g. propranolol)
Type III
Amiodarone
Dronedarone
Bretylium
Dofetilide
Ibutilide
Sotalol
Type IV
Nondihydropyridine calcium channel antagonist (verapamil and diltiazem)
Table includes compounds introduced after publication of the original classification.
82
Glossary
ACEI
ACS
AF
Atrial fibrillation
AFl
Atrial Flutter
AFFIRM
AP
Accessory Pathway
AV
Atrioventricular
ARB
BAFTA
bpm
CCB
CHA2DS2VASc
CHADS2
CHF
COPD
CPR
Cardiopulmonary Resuscitation
CRT
CT
Computed tomography
CV
Cardioversion
CYP
Cytochrome P
DCCV
DM
Diabetes Mellitus
EAPCI
ECG
Electrocardiogram
EHRA
GPI
HAS-BLED
HCM
Hypertrophic Cardiomyopathy
HF
Heart Failure
HOT CAF
HTN
Hypertension
ICD
INR
IV
Intravenous
J-RHYTHM
LA
Left atrium
LAA
LMWH
LoE
Level of Evidence
LV
Left ventricle
LVEF
LVH
MI
Myocardial Infarction
N/A
Not available
ND
Not Determined
NYHA
OAC
Oral Anticoagulant
PAD
PAF
PCI
Percutaneous Intervention
PIAF
PUFA
PVI
RACE
RE-LY
SCD
SR
Sinus Rhythm
STAF
TE
Thromboembolism
TE risk
Thrombo-embolic risk
TIA
TOE
Transesophageal echocardiogram
TTE
Transthoracic echocardiogram
UFH
Unfractionated Heparin
VHD
VKA
Vitamin K Antagonist
VTE
WPW
Wolff-Parkinson-White Syndrome
84
85
(14) Fitzmaurice DA, Hobbs FD, Jowett S, Mant J, Murray ET, Holder R, Raftery
JP,Bryan S, Davies M, Lip GY, Allan TF. Screening versus routine practice in detection
of atrial fibrillation in patients aged 65 or over: cluster randomised controlledtrial. BMJ
2007;335:383.
(15) Dorian P, Guerra PG, Kerr CR, ODonnell SS, Crystal E, Gillis AM, Mitchell LB, Roy
D, Skanes AC, Rose MS, Wyse DG. Validation of a new simple scale to measure
symptoms in atrial fibrillation: the Canadian Cardiovascular Society Severity in Atrial
Fibrillation scale. Circ Arrhythm Electrophysiol 2009;2:218224.
(16) Kirchhof P, Bax J, Blomstrom-Lundquist C, Calkins H, Camm AJ, Cappato R, Cosio
F, Crijns H, Diener HC, Goette A, Israel CW, Kuck KH, Lip GY, Nattel S, Page RL,
Ravens U, Schotten U, Steinbeck G, Vardas P, Waldo A, Wegscheider K, Willems S,
Breithardt G. Early and comprehensive management
nd
of atrial fibrillation: executive summary of the proceedings from the 2 AFNET-EHRA
consensus conference Research perspectives in AF. Eur Heart J 2009;30:p2969
2977c.
(17) Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, PooleWilson PA, Stromberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A,
Nieminen M, Priori SG, Swedberg K, Vahanian A, Camm J, De Caterina R, Dean V,
Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S,
Tendera M, Widimsky P, Zamorano JL. ESC Guidelines for the diagnosis and treatment
of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment
of
Acute and Chronic Heart Failure 2008 of the European Society of Cardiology.
Developed in collaboration with the Heart Failure Association of the ESC (HFA) and
endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J
2008;29:23882442.
(18) Calkins H, Brugada J, Packer DL, Cappato R, Chen SA, Crijns HJ, Damiano RJ Jr,
Davies DW, Haines DE, Haissaguerre M, Iesaka Y, Jackman W, Jais P, Kottkamp H,
Kuck KH, Lindsay BD, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee
K, Natale A, Pappone C, Prystowsky E, Raviele A, Ruskin JN, Shemin RJ, Calkins H,
Brugada J, Chen SA, Prystowsky EN, Kuck KH, Natale A, Haines DE, Marchlinski FE,
Calkins H, Davies DW, Lindsay BD, McCarthy PM, Packer DL, Cappato R, Crijns HJ,
Damiano RJ Jr, Haissaguerre M, Jackman WM, Jais P, Iesaka Y, Kottkamp H, Mont L,
Morady F, Nademanee K, Pappone C, Raviele A, Ruskin JN, Shemin RJ.
HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of
Atrial Fibrillation: Recommendations for Personnel, Policy, Procedures and Follow-Up: a
report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation
of Atrial Fibrillation developed in partnership with the European Heart Rhythm
Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in
collaboration with the American College of Cardiology (ACC), American Heart
Association (AHA), and the Society of Thoracic
Surgeons (STS). Endorsed and approved by the governing bodies of the American
College of Cardiology, the American Heart Association, the European Cardiac
Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic
Surgeons, and the Heart Rhythm Society. Europace 2007;9:335379.
(19) Jabaudon D, Sztajzel J, Sievert K, Landis T, Sztajzel R. Usefulness of ambulatory
7-day ECG monitoring for the detection of atrial fibrillation and flutter after acute stroke
and transient ischemic attack. Stroke 2004;35:16471651.
(20) Haverkamp W, Breithardt G, Camm AJ, Janse MJ, Rosen MR, Antzelevitch C,
Escande D, Franz M, Malik M, Moss A, Shah R. The potential for QT prolongation and
proarrhythmia by non-antiarrhythmic drugs: clinical and regulatory implications. Report
on a policy conference of the European Society of Cardiology. Eur Heart J
2000;21:12161231.
86
(21) Singh BN, Singh SN, Reda DJ, Tang XC, Lopez B, Harris CL, Fletcher RD, Sharma
SC, Atwood JE, Jacobson AK, Lewis HD Jr, Raisch DW, Ezekowitz MD. Amiodarone
versus sotalol for atrial fibrillation. N Engl J Med 2005;352:18611872.
(22) Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillationPharmacological Intervention in Atrial Fibrillation (PIAF): a randomized trial. Lancet
2000;356:17891794.
(23) AFFIRM Investigators. A comparison of rate control and rhythm control in patients
with atrial fibrillation. N Engl J Med 2002;347:18251833.
(24) Van Gelder IC, Hagens VE, Bosker HA, Kingma H, Kamp O, Kingma T, Said SA,
Darmanata JI, Timmermanns AJM, Tijssen JGP, Crijns HJ. A comparison of rate control
and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med
2002;347:18341840.
(25) Carlsson J, Miketic S, Windeler J, Cuneo A, Haun S, Micus S, Walter S, Tebbe U,
and the STAF Investigators. Randomized trial of rate-control versus rhythmcontrol in
persistent atrial fibrillation. J Am Coll Cardiol 2003;41:16901696.
(26) Opolski G, Torbicki A, Kosior DA, Szulc M,Wozakowska-Kaplon B, Kolodziej P,
Achremczyk P. Rate control vs rhythm control in patients with nonvalvular persistent
atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT
CAFE) Study. Chest 2004;126:476486.
(27) Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, Bourassa MG, Arnold JM,
Buxton AE, Camm AJ, Connolly SJ, Dubuc M, Ducharme A, Guerra PG, Hohnloser SH,
Lambert J, Le Heuzey JY, OHara G,
Pedersen OD, Rouleau JL, Singh BN, Stevenson LW, Stevenson WG, Thibault B,
Waldo AL. Rhythm control versus rate control for atrial fibrillation and heart failure. N
Engl J Med 2008;358:26672677.
(28) Ogawa S, Yamashita T, Yamazaki T, Aizawa Y, Atarashi H, Inoue H, Ohe T, Ohtsu
H, Okumura K, Katoh T, Kamakura S, Kumagai K, Kurachi Y, Kodama I, Koretsune Y,
Saikawa T, Sakurai M, Sugi K, Tabuchi T, Nakaya H, Nakayama T, Hirai M, Fukatani M,
Mitamura H. Optimal treatment strategy
for patients with paroxysmal atrial fibrillation: J-RHYTHM Study. Circ J 2009; 73:242
248.
(29) Hsu LF, Jais P, Sanders P, Garrigue S, Hocini M, Sacher F, Takahashi Y, Rotter M,
Pasquie JL, Scavee C, Bordachar P, Clementy J, Haissaguerre M. Catheter ablation for
atrial fibrillation in congestive heart failure. N Engl J Med 2004;351:23732383.
(30) Khan MN, Jais P, Cummings J, Di Biase L, Sanders P, Martin DO, Kautzner J, Hao
S, Themistoclakis S, Fanelli R, Potenza D, Massaro R, Wazni O, Schweikert R, Saliba
W, Wang P, Al-Ahmad A, Beheiry S, Santarelli P, Starling RC, Dello Russo A,
Pelargonio G, Brachmann J, Schibgilla V, Bonso A, Casella M, Raviele A, Haissaguerre
M, Natale A. Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. N
Engl J Med 2008;359:17781785.
(31) Wilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, Macle L,
Daoud EG, Calkins H, Hall B, Reddy V, Augello G, Reynolds MR, Vinekar C, Liu CY,
Berry SM, Berry DA. Comparison of antiarrhythmic drug therapy and radiofrequency
catheter ablation in patients with paroxysmal atrial fibrillation:a randomized controlled
trial. JAMA 2010;303:333340.
(32) Talajic M, Khairy P, Levesque S, Connolly SJ, Dorian P, Dubuc M, Guerra PG,
Hohnloser SH, Lee KL, Macle L, Nattel S, Pedersen OD, Stevenson LW, Thibault B,
Waldo AL, Wyse DG, Roy D. Maintenance of sinus rhythm and survival in patients with
heart failure and atrial fibrillation. J Am Coll Cardiol 2010;55:17961802.
87
(33) UK Resuscitation Council. Advanced Life Support (ALS) Provider Manual (4th
edition) London:
Resuscitation Council (UK) Trading Ltd;2004.
(34) Segal JB, McNamara RL, Miller MR, Kim N, Goodman SN, Powe NR, Robinson K,
Yu D, Bass EB. The evidence regarding the drugs used for ventricular rate control. J
Fam Pract 2000;49:4759.
(35) Hou ZY, Chang MS, Chen CY, Tu MS, Lin SL, Chiang HT, Woosley RL. Acute
treatment of recent-onset atrial fibrillation and flutter with a tailored dosing regimen of
intravenous amiodarone. A randomized, digoxin-controlled study. Eur Heart J
1995;16:521528.
(36) Reisinger J, Gatterer E, LangW, Vanicek T, Eisserer G, Bachleitner T, Niemeth C,
Aicher F, Grander W, Heinze G, Kuhn P, Siostrzonek P. Flecainide versus ibutilide for
immediate cardioversion of atrial fibrillation of recent onset. Eur Heart J 2004;25:1318
1324.
(37) Khan IA. Single oral loading dose of propafenone for pharmacological
cardioversion of recent-onset atrial fibrillation. J Am Coll Cardiol 2001;37:542547.
(38) Martinez-Marcos FJ, Garcia-Garmendia JL, Ortega-Carpio A, Fernandez-Gomez
JM, Santos JM, Camacho C. Comparison of intravenous flecainide, propafenone, and
amiodarone for conversion of acute atrial fibrillation to sinus rhythm. Am J Cardiol
2000;86:950953.
(39) Chevalier P, Durand-Dubief A, Burri H, Cucherat M, Kirkorian G, Touboul P.
Amiodarone versus placebo and class Ic drugs for cardioversion of recent-onset atrial
fibrillation: a meta-analysis. J Am Coll Cardiol 2003;41:255262.
(40) Vardas PE, Kochiadakis GE, Igoumenidis NE, Tsatsakis AM, Simantirakis EN,
Chlouverakis GI. Amiodarone as a first-choice drug for restoring sinus rhythm in
patients with atrial fibrillation: a randomized, controlled study. Chest 2000;117:1538
1545.
(41) Bianconi L, Castro A, Dinelli M, Alboni P, Pappalardo A, Richiardi E, Santini M.
Comparison of intravenously administered dofetilide versus amiodarone in the acute
termination of atrial fibrillation and flutter. A multicentre, randomized, double-blind,
placebo-controlled study. Eur Heart J 2000;21:12651273.
(42) Alboni P, Botto GL, Baldi N, Luzi M, Russo V, Gianfranchi L, Marchi P, Calzolari M,
Solano A, Baroffio R, Gaggioli G. Outpatient treatment of recent-onset atrial fibrillation
with the pill-in-the-pocket approach. N Engl J Med 2004;351:23842391.
(43) Kirchhof P, Eckardt L, Loh P, Weber K, Fischer RJ, Seidl KH, Bocker D, Breithardt
G, Haverkamp W, Borggrefe M. Anteriorposterior versus anteriorlateral electrode
positions for external cardioversion of atrial fibrillation:a randomised trial. Lancet
2002;360:12751279.
(44) Oral H, Souza JJ, Michaud GF, Knight BP, Goyal R, Strickberger SA, Morady
F.Facilitating transthoracic cardioversion of atrial fibrillation with ibutilide pretreatment. N
Engl J Med 1999;340:18491854.
(45) Manios EG, Mavrakis HE, Kanoupakis EM, Kallergis EM, Dermitzaki DN,
Kambouraki DC, Vardas PE. Effects of amiodarone and diltiazem on persistent atrial
fibrillation conversion and recurrence rates: a randomized controlled study. Cardiovasc
Drugs Ther 2003;17:3139.
(46) Bianconi L, Mennuni M, Lukic V, Castro A, Chieffi M, Santini M. Effects of oral
propafenone administration before electrical cardioversion of chronic atrial fibrillation: a
placebo-controlled study. J Am Coll Cardiol 1996;28:700706.
88
89
(62) Connolly SJ, Laupacis A, Gent M, et al. Canadian Atrial Fibrillation Anticoagulation
(62) Connolly
Laupacis
A, Gent
M, et al. Canadian
Atrial Fibrillation Anticoagulation
(CAFA)
Study.SJ,
J Am
Coll Cardiol
1991;18:349
55.
(CAFA) Study. J Am Coll Cardiol 1991;18:349 55.
(63) Ezekowitz MD, Bridgers SL, James KE, et al. Warfarin in the prevention of stroke
(63)
Ezekowitz
Bridgers SL,
James
KE, et al. Warfarin
in theStroke
prevention
of stroke
associated
withMD,
nonrheumatic
atrial
fibrillation.Veterans
Affairs
Prevention
in
associated with
nonrheumatic
Nonrheumatic
Atrial
Fibrillation atrial fibrillation.Veterans Affairs Stroke Prevention in
Nonrheumatic[published
Atrial Fibrillation
Investigators
erratum appears in N Engl J Med 1993; 328(2):148]. N Engl J
Investigators
[published
Med
1992;327:1406
12.erratum appears in N Engl J Med 1993; 328(2):148]. N Engl J
Med 1992;327:1406 12.
(64) Singer DE, Albers GW, Dalen JE, Fang MC, Go AS, Halperin JL, Lip GY, Manning
(64) Singer
DE, Albers
GW, in
Dalen
Fang MC,American
Go AS, Halperin
Lip GY,
Manning
WJ.
Antithrombotic
therapy
atrialJE,
fibrillation:
College JL,
of Chest
Physicians
WJ. Antithrombotic
therapy
in atrial
fibrillation:
College
of Chest Physicians
Evidence-Based
Clinical
Practice
Guidelines
(8thAmerican
Edition). Chest
2008;133:546S592S
Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:546S592S
(65) Lip GY, Golding DJ, Nazir M, Beevers DG, Child DL, Fletcher RI. A survey of atrial
(65) Lip GY,
Golding practice:
DJ, Nazirthe
M, West
Beevers
DG, ChildAtrial
DL, Fletcher
RI.Project.
A surveyBrofJ atrial
fibrillation
in general
Birmingham
Fibrillation
Gen
fibrillation
in general practice: the West Birmingham Atrial Fibrillation Project. Br J Gen
Pract
1997;47:285289.
Pract 1997;47:285289.
(66) Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, Flachskampf
(66)
Vahanian
H, Bax
Butchart
Dion R,L,Filippatos
G,Guidelines
Flachskampf
F,
Hall
R, Iung A,
B, Baumgartner
Kasprzak J, Nataf
P,J,Tornos
P, E,
Torracca
Wenink A.
on
F, Hall
R, Iung B, Kasprzak
Nataf disease:
P, Tornosthe
P, Torracca
L, Wenink
Guidelines on
the
management
of valvularJ, heart
Task Force
on the A.
Management
of
the management
of valvular
disease: the
Task Force
on the Management
Valvular
Heart Disease
of heart
the European
Society
of Cardiology.
Eur Heart of
J
Valvular Heart Disease of the European Society of Cardiology. Eur Heart J
2007;28:230268.
2007;28:230268.
(67) Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, Seward
(67) Tsang
Miyasaka
Barnes ME,
Gersh
BJ, Cha SS,
Baileyfibrillation
KR, Abhayaratna
WP, County,
Seward
JB,
TS.Y,Secular
trends
in incidence
of atrial
in Olmsted
JB, Tsang TS.
in incidenceonof the
atrial
fibrillationforin future
Olmsted
County,
Minnesota,
1980Secular
to 2000,trends
and implications
projections
prevalence.
Minnesota, 2006;114:119125.
1980 to 2000, and implications on the projections for future prevalence.
Circulation
Circulation 2006;114:119125.
(68) Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY, Murray E. Warfarin
(68) Mant
J, Hobbs
FD, Fletcher
K, Roalfe
A, Fitzmaurice
D, Lip GY,
Murray E.with
Warfarin
versus
aspirin
for stroke
prevention
in an
elderly community
population
atrial
versus
aspirin
for stroke prevention
in an Treatment
elderly community
population
with atrial
fibrillation
(the Birmingham
Atrial Fibrillation
of the Aged
Study, BAFTA):
a
fibrillation (the
Birmingham
Atrial Fibrillation
Treatment of the Aged Study, BAFTA): a
randomised
controlled
trial. Lancet
2007;370:493503.
randomised controlled trial. Lancet 2007;370:493503.
(69) Sato H, Ishikawa K, Kitabatake A, Ogawa S, Maruyama Y, Yokota Y, Fukuyama T,
(69)Y,
Sato
H, Ishikawa
K, Kitabatake
A, Ogawa
S, Maruyama
Y, K,
Yokota
Y, Fukuyama
T,
Doi
Mochizuki
S, Izumi
T, Takekoshi
N, Yoshida
K, Hiramori
Origasa
H, Uchiyama
DoiMatsumoto
Y, Mochizuki
Izumi T, Takekoshi
N, Low-dose
Yoshida K,aspirin
Hiramori
Origasa H,ofUchiyama
S,
M,S,Yamaguchi
T, Hori M.
forK,prevention
stroke in
S, Matsumoto
M, with
Yamaguchi
T, Hori M.Japan
Low-dose
for prevention
of stroke
in
low-risk
patients
atrial fibrillation:
Atrialaspirin
Fibrillation
Stroke Trial.
Stroke
low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial. Stroke
2006;37:447451.
2006;37:447451.
(70) Maisel WH. Autonomic modulation preceding the onset of atrial fibrillation. J Am
(70) Cardiol
Maisel 2003;42:1269
WH. Autonomic
modulation preceding the onset of atrial fibrillation. J Am
Coll
70.
Coll Cardiol 2003;42:1269 70.
(71) Israel CW, Gronefeld G, Ehrlich JR, et al. Long-term risk of recurrent atrial
(71)
IsraelasCW,
Gronefeld
JR, monitoring
et al. Long-term
of recurrent
atrial
fibrillation
documented
by G,
an Ehrlich
implantable
device: risk
implications
for optimal
fibrillation
as Jdocumented
by an
implantable monitoring device: implications for optimal
patient
care.
Am Coll Cardiol
2004;43:4752.
patient care. J Am Coll Cardiol 2004;43:4752.
(72) Page RL, Wilkinson WE, Clair WK, et al. Asymptomatic arrhythmias in patients with
(72) Page RL,paroxysmal
Wilkinson WE,
WK, etand
al. Asymptomatic
arrhythmias in patients
with
symptomatic
atrialClair
fibrillation
paroxysmal supraventricular
tachycardia.
symptomatic
paroxysmal7.
atrial fibrillation and paroxysmal supraventricular tachycardia.
Circulation 1994;89:224
Circulation 1994;89:224 7.
(73) Page RL, Tilsch TW, Connolly SJ, et al. Asymptomatic or silent atrial fibrillation:
(73) Page RL,
TW, Connolly
et al.
Asymptomatic
or silent
atrial Circulation
fibrillation:
frequency
in Tilsch
untreated
patients SJ,
and
patients
receiving
azimilide.
frequency in untreated patients and patients receiving azimilide. Circulation
2003;107:11415.
2003;107:11415.
(74) Kumagai K, Nakashima H, Urata H, et al. Effects of angiotensin II type 1 receptor
(74) Kumagai
Nakashima
H, Urata H,
et al. Effects
of angiotensin
typeColl
1 receptor
antagonist
on K,
electrical
and structural
remodeling
in atrial
fibrillation. JII Am
Cardiol
antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol
2003;41:2197204.
2003;41:2197204.
(75) Herweg B, Dalal P, Nagy B, et al. Power spectral analysis of heart period variability
(75)
Herweg B,
Dalal
P, Nagy
B, etinitiation
al. Power
spectral analysis
heart period
of
preceding
sinus
rhythm
before
of paroxysmal
atrial of
fibrillation.
Am variability
J Cardiol
of preceding 74.
sinus rhythm before initiation of paroxysmal atrial fibrillation. Am J Cardiol
1998;82:869
1998;82:869 74.
90
(76) Kerr CR, Boone J, Connolly SJ, et al. The Canadian Registry of Atrial Fibrillation: a
noninterventional follow-up of patients after the first diagnosis of atrial fibrillation. Am J
Cardiol 1998;82:82N5N.
(77) The Stroke Prevention in Atrial Fibrillation Investigators. Predictors of
thromboembolism in atrial fibrillation: II. Echocardiographic features of patients at risk.
Ann Intern Med 1992;116:6 12.
(78) Heart rate variability: standards of measurement, physiological interpretation and
clinical use. Task Force of the European Society of Cardiology and the North American
Society of Pacing and Electrophysiology. Circulation 1996;93:1043 65.
(79) Frustaci A, Chimenti C, Bellocci F, et al. Histological substrate of atrial biopsies in
patients with lone atrial fibrillation. Circulation 1997;96:11804.
(80) Tsai LM, Lin LJ, Teng JK, et al. Prevalence and clinical significance of left atrial
thrombus in nonrheumatic atrial fibrillation. Int J Cardiol 1997;58:1639.
(81) Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, Mullin CM,
Sick P. Percutaneous closure of the left atrial appendage versus warfarin therapy for
prevention of stroke in patients with atrial fibrillation: a randomised noninferiority trial.
Lancet 2009;374:534542.
(82) Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel
userfriendly score (HAS-BLED) to assess one-year risk of major bleeding in atrial
fibrillation patients: The Euro Heart Survey. Chest 2010; March 18 [Epub ahead of print].
(83) Fang MC, Go AS, Hylek EM, Chang Y, Henault LE, Jensvold NG, Singer DE. Age
and the risk of warfarin-associated hemorrhage: the anticoagulation and risk factors in
atrial fibrillation study. J Am Geriatr Soc 2006;54:12311236.
(84) Van Gelder IC, Groenveld HF, Crijns HJ, Tuininga YS, Tijssen JG, Alings AM,
Hillege HL, Bergsma-Kadijk JA, Cornel JH, Kamp O, Tukkie R, Bosker HA, Van
Veldhuisen DJ, Van den Berg MP. Lenient versus strict rate control in patients with atrial
fibrillation. N Engl J Med 2010;362:13631373.
(85) Hohnloser SH, Crijns HJ, van Eickels M, Gaudin C, Page RL, Torp-Pedersen
C,Connolly SJ. Effect of dronedarone on cardiovascular events in atrial fibrillation. N
Engl J Med 2009;360:668678.
(86) Singh BN, Connolly SJ, Crijns HJ, Roy D, Kowey PR, Capucci A, Radzik D, Aliot
EM, Hohnloser SH. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or
flutter. N Engl J Med 2007;357:987999.
(87) Davy JM, Herold M, Hoglund C, Timmermans A, Alings A, Radzik D, Van Kempen
L. Dronedarone for the control of ventricular rate in permanent atrial fibrillation: the
Efficacy and safety of dRonedArone for the cOntrol of ventricular rate during atrial
fibrillation (ERATO) study. Am Heart J 2008;156:527.e1527.e9.
(88) Murgatroyd FD, Gibson SM, Baiyan X, ONunain S, Poloniecki JD, Ward DE, Malik
M, Camm AJ. Double-blind placebo-controlled trial of digoxin in symptomatic
paroxysmal atrial fibrillation. Circulation 1999;99:27652770.
(89) Farshi R, Kistner D, Sarma JS, et al. Ventricular rate control in chronic atrial
fibrillation during daily activity and programmed exercise: a crossover open-label study
of five drug regimens. J Am Coll Cardiol 1999;33:304 10.
(90) Ozcan C, Jahangir A, Friedman PA, Patel PJ, Munger TM, Rea RF, Lloyd MA,
Packer DL, Hodge DO, Gersh BJ, Hammill SC, Shen WK. Long-term survival after
ablation of the atrioventricular node and implantation of a permanent pacemaker in
patients with atrial fibrillation. N Engl J Med 2001;344:10431051.
91
92
(114) Van Gelder IC, Crijns HJ, Van Gilst WH, Van Wijk LM, Hamer HP, Lie KI. Efficacy
and safety of flecainide acetate in the maintenance of sinus rhythm after electrical
cardioversion of chronic atrial fibrillation or atrial flutter. Am J Cardiol 1989;64:1317
1321.
(115) Singh SN, Fletcher RD, Fisher SG, Singh BN, Lewis HD, Deedwania PC, Massie
BM, Colling C, Lazzeri D. Amiodarone in patients with congestive heart failure and
asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in
Congestive Heart Failure. N Engl J Med 1995;333:7782.
(116) Singh D, Cingolani E, Diamon GA, Kaul S. Dronedarone for atrial fibrillation: have
we expanded the antiarrhythmic armamentarium. J Am Coll Cardiol 2010;55:15691576.
(117) Calkins H, Reynolds MR, Spector P, Sondhi M, Xu Y, Martin A, Williams CJ,
Sledge I. Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency
ablation: two systematic literature reviews and meta-analyses. Circ Arrhythm
Electrophysiol 2009;2:349361.
(118) Wazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, SalibaW, Bash D,
Schweikert R, Brachmann J, Gunther J, Gutleben K, Pisano E, Potenza D, Fanelli R,
Raviele A, Themistoclakis S, Rossillo A, Bonso A, Natale A. Radiofrequency ablation vs
antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a
randomized trial. JAMA 2005;293:26342640.
(119) Gaita F, Riccardi R, Caponi D, Shah D, Garberoglio L, Vivalda L, Dulio A,
Chiecchio A, Manasse E, Gallotti R. Linear cryoablation of the left atrium versus
pulmonary vein cryoisolation in patients with permanent atrial fibrillation and valvular
heart disease: correlation of electroanatomic mapping and longterm clinical results.
Circulation 2005;111:136142.
(120) Cox JL, Boineau JP, Schuessler RB, Ferguson TB Jr, Cain ME, Lindsay BD, Corr
PB, Kater KM, Lappas DG. Successful surgical treatment of atrial fibrillation. Review
and clinical update. JAMA 1991;266:19761980.
(121) Noheria A, Kumar A, Wylie JV Jr, Josephson ME. Catheter ablation vs
antiarrhythmic drug therapy for atrial fibrillation: a systematic review. Arch Intern Med
2008;168:581586.
(122) Jais P, Cauchemez B, Macle L, Daoud E, Khairy P, Subbiah R, Hocini M,
Extramiana F, Sacher F, Bordachar P, Klein G, Weerasooriya R, Clementy J,
Haissaguerre M. Catheter ablation versus antiarrhythmic drugs for atrial fibrillation:the
A4 study. Circulation 2008;118:24982505.
(123) Pappone C, Augello G, Sala S, Gugliotta F, Vicedomini G, Gulletta S, Paglino G,
Mazzone P, Sora N, Greiss I, Santagostino A, LiVolsi L, Pappone N, Radinovic A,
Manguso F, Santinelli V. A randomized trial of circumferential pulmonary vein ablation
versus antiarrhythmic drug therapy in paroxysmal atrial fibrillation:the APAF Study. J
Am Coll Cardiol 2006;48:23402347.
(124) Piccini JP, Lopes RD, Kong MH, Hasselblad V, Jackson K, Al-Khatib SM.
Pulmonary vein isolation for the maintenance of sinus rhythm in patients with atrial
fibrillation: a meta-analysis of randomized, controlled trials. Circ Arrhythm Electrophysiol
2009;2:626633.
(125) Nair GM, Nery PB, Diwakaramenon S, Healey JS, Connolly SJ, Morillo CA. A
systematic review of randomized trials comparing radiofrequency ablation with
antiarrhythmic medications in patients with atrial fibrillation. J Cardiovasc Electrophysiol
2009;20:138144.
93
94
(141) Wachtell K, Lehto M, Gerdts E, Olsen MH, Hornestam B, Dahlof B, Ibsen H, Julius
S, Kjeldsen SE, Lindholm LH, Nieminen MS, Devereux RB. Angiotensin II receptor
blockade reduces new-onset atrial fibrillation and subsequent stroke compared to
atenolol: the Losartan Intervention For End Point Reduction in Hypertension (LIFE)
study. J Am Coll Cardiol 2005;45:712719.
(142) Schmieder RE, Kjeldsen SE, Julius S, McInnes GT, Zanchetti A, Hua TA.
Reduced incidence of new-onset atrial fibrillation with angiotensin II receptor
blockade:the VALUE trial. J Hypertens 2008;26:403411.
(143) Madrid AH, Bueno MG, Rebollo JM, Marin I, Pena G, Bernal E, Rodriguez A,
Cano L, Cano JM, Cabeza P, Moro C. Use of irbesartan to maintain sinus rhythm in
patients with long-lasting persistent atrial fibrillation: a prospective and randomized
study. Circulation 2002;106:331336.
(144) Ueng KC, Tsai TP, Yu WC, Tsai CF, Lin MC, Chan KC, Chen CY, Wu DJ, Lin CS,
Chen SA. Use of enalapril to facilitate sinus rhythm maintenance after external
cardioversion of long-standing persistent atrial fibrillation. Results of a prospective and
controlled study. Eur Heart J 2003;24:20902098.
(145) Tveit A, Seljeflot I, Grundvold I, Abdelnoor M, Smith P, Arnesen H. Effect of
candesartan and various inflammatory markers on maintenance of sinus rhythm after
electrical cardioversion for atrial fibrillation. Am J Cardiol 2007;99:15441548.
(146) Yin Y, Dalal D, Liu Z, Wu J, Liu D, Lan X, Dai Y, Su L, Ling Z, She Q, Luo K, Woo
K, Dong J. Prospective randomized study comparing amiodarone vs. amiodarone plus
losartan vs. amiodarone plus perindopril for the prevention of atrial fibrillation recurrence
in patients with lone paroxysmal atrial fibrillation. Eur Heart J 2006;27:18411846.
(147) Belluzzi F, Sernesi L, Preti P, Salinaro F, Fonte ML, Perlini S. Prevention of
recurrent lone atrial fibrillation by the angiotensin-II converting enzyme inhibitor ramipril
in normotensive patients. J Am Coll Cardiol 2009;53:2429.
(148) Liakopoulos OJ, Choi YH, Kuhn EW, Wittwer T, Borys M, Madershahian N,
Wassmer G, Wahlers T. Statins for prevention of atrial fibrillation after cardiac surgery: a
systematic literature review. J Thorac Cardiovasc Surg 2009;138:678686 e1.
(149) Savelieva I, Kourliouros A, Camm J. Primary and secondary prevention of atrial
fibrillation with statins and polyunsaturated fatty acids: review of evidence and clinical
relevance. Naunyn Schmiedebergs Arch Pharmacol 2010;381:113.
(150) Patti G, Chello M, Candura D, Pasceri V, DAmbrosio A, Covino E, Di Sciascio G.
Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in
patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for
Reduction of MYocardial Dysrhythmia After cardiac surgery) study. Circulation
2006;114:14551461.
(151) Fauchier L, Pierre B, de Labriolle A, Grimard C, Zannad N, Babuty D.
Antiarrhythmic effect of statin therapy and atrial fibrillation: a meta-analysis of
randomized controlled trials. J Am Coll Cardiol 2008;51:828835.
(152) Liu T, Li L, Korantzopoulos P, Liu E, Li G. Statin use and development of atrial
fibrillation: a systematic review and meta-analysis of randomized clinical trials and
observational studies. Int J Cardiol 2008;126:160170.
(153) Crystal E, Garfinkle MS, Connolly SS, Ginger TT, Sleik K, Yusuf SS. Interventions
for preventing post-operative atrial fibrillation in patients undergoing heart surgery.
Cochrane Database Syst Rev 2004;4:CD003611.
(154) Burgess DC, Kilborn MJ, Keech AC. Interventions for prevention of postoperative
atrial fibrillation and its complications after cardiac surgery: a meta-analysis. Eur Heart J
2006;27:28462857.
95
(155) Mathew JP, Fontes ML, Tudor IC, Ramsay J, Duke P, Mazer CD, Barash PG, Hsu
PH, Mangano DT. A multicenter risk index for atrial fibrillation after cardiac surgery.
JAMA 2004;291:17201729.
(156) Patel AA, White CM, Gillespie EL, Kluger J, Coleman CI. Safety of amiodarone in
the prevention of postoperative atrial fibrillation: a meta-analysis. Am J Health Syst
Pharm 2006;63:829837.
(157) Ho KM, Tan JA. Benefits and risks of corticosteroid prophylaxis in adult cardiac
surgery: a doseresponse meta-analysis. Circulation 2009;119:18531866.
(158) Dunning J, Treasure T, Versteegh M, Nashef SA. Guidelines on the prevention
and management of de novo atrial fibrillation after cardiac and thoracic surgery. Eur J
Cardiothorac Surg 2006;30:852872.
(159) Daoud EG. Management of atrial fibrillation in the post-cardiac surgery setting.
Cardiol Clin 2004;22:159166.
(160) Bagshaw SM, Galbraith PD, Mitchell LB, Sauve R, Exner DV, Ghali WA.
Prophylactic amiodarone for prevention of atrial fibrillation after cardiac surgery: a metaanalysis. Ann Thorac Surg 2006;82:19271937.
(161) Wells JL Jr, MacLean WA, James TN, et al. Characterization of atrial flutter.
Studies in man after open heart surgery using fixed atrial electrodes. Circulation
1979;60:66573.
(162) Schmitt J, Duray G, Gersh BJ, Hohnloser SH. Atrial fibrillation in acute myocardial
infarction: a systematic review of the incidence, clinical features and prognostic
implications. Eur Heart J 2009;30:10381045.
(163) Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH,
Arensberg D, Baker A, Friedman L, Greene HL, Huther ML, Richardson DW,
Investigators and the CAST investigators. Mortality and morbidity in patients receiving
encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression
Trial. N Engl J Med 1991;324:781788.
(164) Blomstrom-Lundqvist C, Scheinman MM, Aliot EM, Alpert JS, Calkins H, Camm
AJ, Campbell WB, Haines DE, Kuck KH, Lerman BB, Miller DD, Shaeffer CW,
Stevenson WG, Tomaselli GF, Antman EM, Smith SC Jr, Faxon DP, Fuster V, Gibbons
RJ, Gregoratos G, Hiratzka LF, Hunt SA, Jacobs AK, Russell RO Jr, Priori SG, Blanc JJ,
Budaj A, Burgos EF, Cowie M,Deckers JW, Garcia MA, Klein WW, Lekakis J, Lindahl B,
Mazzotta G, Morais JC, Oto A, Smiseth O, Trappe HJ. ACC/AHA/ESC guidelines for the
management of patients with supraventricular arrhythmiasexecutive summary. a
report of the American College of Cardiology/American Heart Association task force on
practice guidelines and the European Society of Cardiology committee for practice
guidelines (writing committee to develop guidelines for the management of patients with
supraventricular arrhythmias) developed in collaboration with NASPE-Heart Rhythm
Society. J Am Coll Cardiol 2003;42:149314531.
(165) Wellens HJ. Should catheter ablation be performed in asymptomatic patients with
WolffParkinsonWhite syndrome? When to perform catheter ablation in asymptomatic
patients with a WolffParkinsonWhite electrocardiogram. Circulation 2005;112:2201
2297; discussion 2216.
(166) Pappone C, Santinelli V, Manguso F, Augello G, Santinelli O, Vicedomini G,
Gulletta S, Mazzone P, Tortoriello V, Pappone A, Dicandia C, Rosanio S. A randomized
study of prophylactic catheter ablation in asymptomatic patients with the Wolff
ParkinsonWhite syndrome. N Engl J Med 2003;349:18031811.
(167) Bryg RJ, Gordon PR, Kudesia VS, et al. Effect of pregnancy on pressure gradient
in mitral stenosis. Am J Cardiol 1989;63:3846.
96
(168) Whittemore R, Hobbins JC, Engle MA. Pregnancy and its outcome in women with
and without surgical treatment of congenital heart disease. Am J Cardiol 1982;50:641
51.
(169) Forfar JC, Miller HC, Toft AD. Occult thyrotoxicosis: a correctable cause of
idiopathic atrial fibrillation. Am J Cardiol 1979;44:9 12.
(170) Page RL. Treatment of arrhythmias during pregnancy. Am Heart J 1995;130:871
6.
(171) Cox JL, Gardner MJ. Cardiovascular drugs in pregnancy and lactation. In:
Gleicher N, Gall SA, Sibai BM, et al., editors. Principles and Practice of Medical
Therapy in Pregnancy. Stamford, CT: Appleton&Lange, 1998:91126.
(172) Chow T, Galvin J, McGovern B. Antiarrhythmic drug therapy in pregnancy and
lactation. Am J Cardiol 1998;82:58I 62I.
(173) Wagner X, Jouglard J, Moulin M, et al. Coadministration of flecainide acetate and
sotalol during pregnancy: lack of teratogenic effects, passage across the placenta, and
excretion in human breast milk. Am Heart J 1990;119:700 2.
(174) Vaughan Williams EM. A classification of antiarrhythmic actions reassessed after
a decade of new drugs. J Clin Pharmacol 1984;24:12947.
(175) Lownes HE, Ives TJ. Mexiletine use in pregnancy and lactation. Am J Obstet
Gynecol 1987;157:446 7.
(176) Ovadia M, Brito M, Hoyer GL, et al. Human experience with amiodarone in the
embryonic period. Am J Cardiol 1994;73:316 7.
(177) Magee LA, Downar E, Sermer M, et al. Pregnancy outcome after gestational
exposure to amiodarone in Canada. Am J Obstet Gynecol 1995;172:130711.
(178) Foster CJ, Love HG. Amiodarone in pregnancy. Case report and review of the
literature. Int J Cardiol 1988;20:30716.
(179) Leung CY, Brodsky MA. Cardiac arrhythmias and pregnancy. In: Elkayam U,
Gleicher N, editors. Cardiac Problems in Pregnancy. New York: Wiley-Liss, 1998:155
75.
(180) Bates SM, Greer IA, Pabinger I, Sofaer S, Hirsh J. Venous thromboembolism,
thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest
Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest
2008;133:p844S886S.
(181) Chen MS, McCarthy PM, Lever HM, Smedira NG, Lytle BL. Effectiveness of atrial
fibrillation surgery in patients with hypertrophic cardiomyopathy. Am J Cardiol
2004;93:373375.
(182) Maron BJ, Olivotto I, Bellone P, Conte MR, Cecchi F, Flygenring BP, Casey SA,
Gohman TE, Bongioanni S, Spirito P. Clinical profile of stroke in 900 patients with
hypertrophic cardiomyopathy. J Am Coll Cardiol 2002;39:301307.
(183) Bertini M, Borleffs JW, Delgado V, Ng AA, Piers SR, Shanks M, Antoni LM, Biffi M,
Boriani G, Schalij M, Bax JJ, Van de Veire N. Prediction of atrial fibrillation in patients
with implantable cardioverter-defibrillator and heart failure. Eur J Heart Fail 2010;in
press.
(184) Fauchier L, Grimard C, Pierre B, Nonin E, Gorin L, Rauzy B, Cosnay P, Babuty D,
Charbonnier B. Comparison of beta blocker and digoxin alone and in combination for
97
98
Copyright:
European Society of Cardiology 2010 - All Rights Reserved.
This clinical practice guideline comprises [a] figure[s] from the ESC
Guidelines for the Management of Atrial Fibrillation (ESC Guidelines)
originally published in the English language in the European Heart Journal
2010; 31:2369-2429; by Oxford University Press under licence from the
European Society of Cardiology (ESC). This publication is for personal
and educational use only. No commercial use is authorized. No part of
this publication or the original ESC Guidelines from which it is derived
may be translated or reproduced in any form without written permission
from the ESC. Permission may be obtained upon submission of a written
request to Oxford University Press, the publisher of the European Heart
Journal and the party authorized to handle such permissions by the ESC.
National Heart Association of Malaysia (NHAM), Ministry of Health (MOH)
and the Academy of Medicine Malaysia (AMM) have obtained permission
to publish this guideline and to distribute it to healthcare professionals
within Malaysia.
For permissions, please contact journals.permissions@oup.com
All rights reserved; no part of this publication may be reproduced, stored in
a retrieval system, or transmitted in any form or by any means, electronic,
mechanical, photocopying, recording, or otherwise without the prior written
permission of Oxford University Press or its licensee Oxford Publishing
Limited (OPL).
Disclaimers:
The original ESC Guidelines represent the views of the ESC and were
arrived at after careful consideration of the available evidence at the time
they were written. Health professionals are encouraged to take them fully
into account when exercising their clinical judgment. The ESC Guidelines do
not, however, override the individual responsibility of health professionals to
make appropriate decisions in the circumstances of the individual patients,
in consultation with that patient, and where appropriate and necessary the
patients guardian or carer, including without limitation in relation to the use
and dosage of drugs mentioned in the ESC Guidelines. It is also the health
professionals responsibility to verify the rules and regulations applicable
to drugs and devices at the time of prescription. Oxford University Press,
OPL and the ESC cannot accept any liability whatsoever in respect of any
claim for damages or otherwise arising therefrom.
Please visit: www.escardio.org/guidelines
99
118